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Chromatin dynamics and RNA metabolism are double-edged swords for the maintenance of plant genome integrity

Nature Plants (2024)Cite this article

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Abstract

Maintenance of genome integrity is an essential process in all organisms. Mechanisms avoiding the formation of DNA lesions or mutations are well described in animals because of their relevance to human health and cancer. In plants, they are of growing interest because DNA damage accumulation is increasingly recognized as one of the consequences of stress. Although the cellular response to DNA damage is mostly studied in response to genotoxic treatments, the main source of DNA lesions is cellular activity itself. This can occur through the production of reactive oxygen species as well as DNA processing mechanisms such as DNA replication or transcription and chromatin dynamics. In addition, how lesions are formed and repaired is greatly influenced by chromatin features and dynamics and by DNA and RNA metabolism. Notably, actively transcribed regions or replicating DNA, because they are less condensed and are sites of DNA processing, are more exposed to DNA damage. However, at the same time, a wealth of cellular mechanisms cooperate to favour DNA repair at these genomic loci. These intricate relationships that shape the distribution of mutations along the genome have been studied extensively in animals but much less in plants. In this Review, we summarize how chromatin dynamics influence lesion formation and DNA repair in plants, providing a comprehensive view of current knowledge and highlighting open questions with regard to what is known in other organisms.

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Fig. 1: Pathways involved in chromatin dynamics or RNA metabolism that influence DNA damage formation or genome maintenance in plants.
Fig. 2: Active DNA demethylation relies on the BER pathway.
Fig. 3: Chromatin features and DNA transactions as sources of DNA damage.
Fig. 4: Several pathways cooperate to avoid DNA damage accumulation associated with RNA metabolism.
Fig. 5: Chromatin modifications and dynamics play central roles in the maintenance of genome integrity.
Fig. 6: RNA metabolism plays a key role in the maintenance of genome integrity.

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References

  1. Tubbs, A. & Nussenzweig, A. Endogenous DNA damage as a source of genomic instability in cancer. Cell 168, 644–656 (2017).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  2. Akakpo, R., Carpentier, M.-C., Ie Hsing, Y. & Panaud, O. The impact of transposable elements on the structure, evolution and function of the rice genome. N. Phytol. 226, 44–49 (2020).

    Article  Google Scholar 

  3. Spampinato, C. P. Protecting DNA from errors and damage: an overview of DNA repair mechanisms in plants compared to mammals. Cell. Mol. Life Sci. 74, 1693–1709 (2017).

    Article  CAS  PubMed  Google Scholar 

  4. Röhrig, S. et al. The RecQ-like helicase HRQ1 is involved in DNA crosslink repair in Arabidopsis in a common pathway with the Fanconi anemia-associated nuclease FAN1 and the postreplicative repair ATPase RAD5A. N. Phytol. 218, 1478–1490 (2018).

    Article  Google Scholar 

  5. Dorn, A. et al. An Arabidopsis FANCJ helicase homologue is required for DNA crosslink repair and rDNA repeat stability. PLoS Genet. 15, e1008174 (2019).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  6. Pedroza-Garcia, J.-A., De Veylder, L. & Raynaud, C. Plant DNA polymerases. Int. J. Mol. Sci. 20, 4814 (2019).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  7. Nisa, M.-U., Huang, Y., Benhamed, M. & Raynaud, C. The plant DNA damage response: signaling pathways leading to growth inhibition and putative role in response to stress conditions. Front. Plant Sci. 10, 653 (2019).

    Article  PubMed  PubMed Central  Google Scholar 

  8. Gentric, N., Genschik, P. & Noir, S. Connections between the cell cycle and the DNA damage response in plants. Int. J. Mol. Sci. 22, 9558 (2021).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  9. Pedroza-Garcia, J. A., Xiang, Y. & De Veylder, L. Cell cycle checkpoint control in response to DNA damage by environmental stresses. Plant J. 109, 490–507 (2022).

    Article  CAS  PubMed  Google Scholar 

  10. Herbst, J., Li, Q.-Q. & De Veylder, L. Mechanistic insights into DNA damage recognition and checkpoint control in plants. Nat. Plants https://doi.org/10.1038/s41477-024-01652-9 (2024).

  11. Biedermann, S. et al. The retinoblastoma homolog RBR1 mediates localization of the repair protein RAD51 to DNA lesions in Arabidopsis. EMBO J. 36, 1279–1297 (2017).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  12. Horvath, B. M. et al. Arabidopsis RETINOBLASTOMA RELATED directly regulates DNA damage responses through functions beyond cell cycle control. EMBO J. 36, 1261–1278 (2017).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  13. Nisa, M. et al. Distinctive and complementary roles of E2F transcription factors during plant replication stress responses. Mol. Plant 16, 1269–1282 (2023).

    Article  CAS  PubMed  Google Scholar 

  14. Shen, H. & Li, Z. DNA double-strand break repairs and their application in plant DNA integration. Genes (Basel) 13, 322 (2022).

    Article  CAS  PubMed  Google Scholar 

  15. Ramsden, D. A., Carvajal-Garcia, J. & Gupta, G. P. Mechanism, cellular functions and cancer roles of polymerase-theta-mediated DNA end joining. Nat. Rev. Mol. Cell Biol. 23, 125–140 (2022).

    Article  CAS  PubMed  Google Scholar 

  16. Cortez, D. Replication-coupled DNA repair. Mol. Cell 74, 866–876 (2019).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  17. Ossowski, S. et al. The rate and molecular spectrum of spontaneous mutations in Arabidopsis thaliana. Science 327, 92–94 (2010).

    Article  CAS  PubMed  Google Scholar 

  18. Lindahl, T. & Karlström, O. Heat-induced depyrimidination of deoxyribonucleic acid in neutral solution. Biochemistry 12, 5151–5154 (1973).

    Article  CAS  PubMed  Google Scholar 

  19. Rochette, P. J. et al. Influence of cytosine methylation on ultraviolet-induced cyclobutane pyrimidine dimer formation in genomic DNA. Mutat. Res. 665, 7–13 (2009).

    Article  CAS  PubMed  Google Scholar 

  20. Johann To Berens, P., Golebiewska, K., Peter, J., Staerck, S. & Molinier, J. UV-B-induced modulation of constitutive heterochromatin content in Arabidopsis thaliana. Photochem. Photobiol. Sci. 22, 2153–2166 (2023).

    Article  CAS  PubMed  Google Scholar 

  21. Manova, V. & Gruszka, D. DNA damage and repair in plants—from models to crops. Front. Plant Sci. 6, 885 (2015).

    Article  PubMed  PubMed Central  Google Scholar 

  22. Morales-Ruiz, T. et al. DEMETER and REPRESSOR OF SILENCING 1 encode 5-methylcytosine DNA glycosylases. Proc. Natl Acad. Sci. USA 103, 6853–6858 (2006).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  23. Du, X. et al. Molecular basis of the plant ROS1-mediated active DNA demethylation. Nat. Plants 9, 271–279 (2023).

    Article  CAS  PubMed  Google Scholar 

  24. Li, J. et al. The Arabidopsis ATR–SOG1 signaling module regulates pleiotropic developmental adjustments in response to 3′-blocked DNA repair intermediates. Plant Cell 34, 852–866 (2022).

    Article  PubMed  Google Scholar 

  25. Kusmartsev, V., Drożdż, M., Schuster-Böckler, B. & Warnecke, T. Cytosine methylation affects the mutability of neighboring nucleotides in germline and soma. Genetics 214, 809–823 (2020).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  26. Shakirov, E. V., Chen, J. J.-L. & Shippen, D. E. Plant telomere biology: the green solution to the end-replication problem. Plant Cell 34, 2492–2504 (2022).

    Article  PubMed  PubMed Central  Google Scholar 

  27. Castillo-González, C., Barbero Barcenilla, B., Young, P. G., Hall, E. & Shippen, D. E. Quantification of 8-oxoG in plant telomeres. Int. J. Mol. Sci. 23, 4990 (2022).

    Article  PubMed  PubMed Central  Google Scholar 

  28. Jia, P., Her, C. & Chai, W. DNA excision repair at telomeres. DNA Repair (Amst.) 36, 137–145 (2015).

    Article  CAS  PubMed  Google Scholar 

  29. Singh, B. N., Sopory, S. K. & Reddy, M. K. Plant DNA topoisomerases: structure, function, and cellular roles in plant development. Crit. Rev. Plant Sci. 23, 251–269 (2004).

    Article  CAS  Google Scholar 

  30. Martinez-Garcia, M., White, C. I., Franklin, F. C. H. & Sanchez-Moran, E. The role of topoisomerase II in DNA repair and recombination in Arabidopsis thaliana. Int. J. Mol. Sci. 22, 13115 (2021).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  31. Li, Q. et al. DNA polymerase ε harmonizes topological states and R-loops formation to maintain genome integrity in Arabidopsis. Nat. Commun. 14, 7763 (2023).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  32. Hartung, F. et al. An archaebacterial topoisomerase homolog not present in other eukaryotes is indispensable for cell proliferation of plants. Curr. Biol. 12, 1787–1791 (2002).

    Article  CAS  PubMed  Google Scholar 

  33. Sugimoto-Shirasu, K. et al. RHL1 is an essential component of the plant DNA topoisomerase VI complex and is required for ploidy-dependent cell growth. Proc. Natl Acad. Sci. USA 102, 18736–18741 (2005).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  34. Kirik, V., Schrader, A., Uhrig, J. F. & Hulskamp, M. MIDGET unravels functions of the Arabidopsis topoisomerase VI complex in DNA endoreduplication, chromatin condensation, and transcriptional silencing. Plant Cell 19, 3100–3110 (2007).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  35. Hacker, L., Dorn, A. & Puchta, H. Repair of DNA–protein crosslinks in plants. DNA Repair (Amst.) 87, 102787 (2020).

    Article  CAS  PubMed  Google Scholar 

  36. Hacker, L., Dorn, A., Enderle, J. & Puchta, H. The repair of topoisomerase 2 cleavage complexes in Arabidopsis. Plant Cell 34, 287–301 (2021).

    Article  PubMed Central  Google Scholar 

  37. Barbour, A. T. & Wuttke, D. S. RPA-like single-stranded DNA-binding protein complexes including CST serve as specialized processivity factors for polymerases. Curr. Opin. Struct. Biol. 81, 102611 (2023).

    Article  CAS  PubMed  Google Scholar 

  38. Aklilu, B. B., Soderquist, R. S. & Culligan, K. M. Genetic analysis of the Replication Protein A large subunit family in Arabidopsis reveals unique and overlapping roles in DNA repair, meiosis and DNA replication. Nucleic Acids Res. 42, 3104–3118 (2014).

    Article  CAS  PubMed  Google Scholar 

  39. Ragland, R. L., Arlt, M. F., Hughes, E. D., Saunders, T. L. & Glover, T. W. Mice hypomorphic for Atr have increased DNA damage and abnormal checkpoint response. Mamm. Genome 20, 375–385 (2009).

    Article  CAS  PubMed  Google Scholar 

  40. Culligan, K. M., Robertson, C. E., Foreman, J., Doerner, P. & Britt, A. B. ATR and ATM play both distinct and additive roles in response to ionizing radiation. Plant J. 48, 947–961 (2006).

    Article  CAS  PubMed  Google Scholar 

  41. Szurman-Zubrzycka, M. et al. ATR, a DNA damage signaling kinase, is involved in aluminum response in barley. Front. Plant Sci. 10, 1299 (2019).

    Article  PubMed  PubMed Central  Google Scholar 

  42. Pedroza-Garcia, J. A. et al. Maize ATR safeguards genome stability during kernel development to prevent early endosperm endocycle onset and cell death. Plant Cell 33, 2662–2684 (2021).

    Article  PubMed  PubMed Central  Google Scholar 

  43. Kaushal, S. & Freudenreich, C. H. The role of fork stalling and DNA structures in causing chromosome fragility. Genes Chromosomes Cancer 58, 270–283 (2019).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  44. Casper, A. M., Nghiem, P., Arlt, M. F. & Glover, T. W. ATR regulates fragile site stability. Cell 111, 779–789 (2002).

    Article  CAS  PubMed  Google Scholar 

  45. Li, S. & Wu, X. Common fragile sites: protection and repair. Cell Biosci. 10, 29 (2020).

    Article  PubMed  PubMed Central  Google Scholar 

  46. Lee, W. T. C. et al. Single-molecule imaging reveals replication fork coupled formation of G-quadruplex structures hinders local replication stress signaling. Nat. Commun. 12, 2525 (2021).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  47. Williams, S. L. et al. Replication-induced DNA secondary structures drive fork uncoupling and breakage. EMBO J. 42, e114334 (2023).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  48. Cagirici, H. B., Budak, H. & Sen, T. Z. Genome-wide discovery of G-quadruplexes in barley. Sci. Rep. 11, 7876 (2021).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  49. Dvořáčková, M., Fojtová, M. & Fajkus, J. Chromatin dynamics of plant telomeres and ribosomal genes. Plant J. 83, 18–37 (2015).

    Article  PubMed  Google Scholar 

  50. Huang, M. et al. Plant 45S rDNA clusters are fragile sites and their instability is associated with epigenetic alterations. PLoS ONE 7, e35139 (2012).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  51. Goffová, I. & Fajkus, J. The rDNA loci—intersections of replication, transcription, and repair pathways. Int. J. Mol. Sci. 22, 1302 (2021).

    Article  PubMed  PubMed Central  Google Scholar 

  52. Akamatsu, Y. & Kobayashi, T. The human RNA Polymerase I transcription terminator complex acts as a replication fork barrier that coordinates the progress of replication with rRNA transcription activity. Mol. Cell. Biol. 35, 1871–1881 (2015).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  53. Gadaleta, M. C. & Noguchi, E. Regulation of DNA replication through natural impediments in the eukaryotic genome. Genes (Basel) 8, 98 (2017).

    Article  PubMed  Google Scholar 

  54. López-Estraño, C., Schvartzman, J. B., Krimer, D. B. & Hernández, P. Characterization of the pea rDNA replication fork barrier: putative cis-acting and trans-acting factors. Plant Mol. Biol. 40, 99–110 (1999).

    Article  PubMed  Google Scholar 

  55. Mozgová, I., Mokros, P. & Fajkus, J. Dysfunction of chromatin assembly factor 1 induces shortening of telomeres and loss of 45S rDNA in Arabidopsis thaliana. Plant Cell 22, 2768–2780 (2010).

    Article  PubMed  PubMed Central  Google Scholar 

  56. Kaya, H. et al. FASCIATA genes for chromatin assembly factor-1 in Arabidopsis maintain the cellular organization of apical meristems. Cell 104, 131–142 (2001).

    Article  CAS  PubMed  Google Scholar 

  57. Muchová, V. et al. Homology-dependent repair is involved in 45S rDNA loss in plant CAF-1 mutants. Plant J. 81, 198–209 (2015).

    Article  PubMed  Google Scholar 

  58. Wear, E. E. et al. Genomic analysis of the DNA replication timing program during mitotic S phase in maize (Zea mays) root tips. Plant Cell 29, 2126–2149 (2017).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  59. Concia, L. et al. Genome-wide analysis of the Arabidopsis replication timing program. Plant Physiol. 176, 2166–2185 (2018).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  60. Nisa, M. et al. The plant DNA polymerase theta is essential for the repair of replication-associated DNA damage. Plant J. 106, 1197–1207 (2021).

    Article  CAS  PubMed  Google Scholar 

  61. Canela, A. et al. Genome organization drives chromosome fragility. Cell 170, 507–521.e18 (2017).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  62. Sun, Y. et al. A graph neural network-based interpretable framework reveals a novel DNA fragility-associated chromatin structural unit. Genome Biol. 24, 90 (2023).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  63. Huang, Y. et al. HSFA1a modulates plant heat stress responses and alters the 3D chromatin organization of enhancer–promoter interactions. Nat. Commun. 14, 469 (2023).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  64. Skourti-Stathaki, K. & Proudfoot, N. J. A double-edged sword: R loops as threats to genome integrity and powerful regulators of gene expression. Genes Dev. 28, 1384–1396 (2014).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  65. Hegazy, Y. A., Fernando, C. M. & Tran, E. J. The balancing act of R-loop biology: the good, the bad, and the ugly. J. Biol. Chem. 295, 905–913 (2020).

    Article  PubMed  Google Scholar 

  66. Petermann, E., Lan, L. & Zou, L. Sources, resolution and physiological relevance of R-loops and RNA–DNA hybrids. Nat. Rev. Mol. Cell Biol. 23, 521–540 (2022).

    Article  CAS  PubMed  Google Scholar 

  67. Yang, Z., Li, M. & Sun, Q. RHON1 co-transcriptionally resolves R-loops for Arabidopsis chloroplast genome maintenance. Cell Rep. 30, 243–256.e5 (2020).

    Article  CAS  PubMed  Google Scholar 

  68. Sun, Q., Csorba, T., Skourti-Stathaki, K., Proudfoot, N. J. & Dean, C. R-loop stabilization represses antisense transcription at the Arabidopsis FLC locus. Science 340, 619–621 (2013).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  69. Gao, J. et al. Toward an understanding of the detection and function of R-loops in plants. J. Exp. Bot. 72, 6110–6122 (2021).

    Article  CAS  PubMed  Google Scholar 

  70. Zhou, J., Zhang, W. & Sun, Q. R-loop: the new genome regulatory element in plants. J. Integr. Plant Biol. 64, 2275–2289 (2022).

    Article  CAS  PubMed  Google Scholar 

  71. Zheng, D., Li, M., Yang, Y., Huang, R. & Zhang, W. R-loops: emerging key regulators in plants. J. Exp. Bot. 74, 2228–2238 (2023).

    Article  CAS  PubMed  Google Scholar 

  72. Li, K. et al. R-loopAtlas: an integrated R-loop resource from 254 plant species sustained by a deep-learning-based tool. Mol. Plant 16, 493–496 (2023).

    Article  CAS  PubMed  Google Scholar 

  73. Yuan, W. et al. ALBA protein complex reads genic R-loops to maintain genome stability in Arabidopsis. Sci. Adv. 5, eaav9040 (2019).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  74. Costantino, L. & Koshland, D. Genome-wide map of R-loop-induced damage reveals how a subset of R-loops contributes to genomic instability. Mol. Cell 71, 487–497.e3 (2018).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  75. Zhou, J. et al. DDM1-mediated R-loop resolution and H2A.Z exclusion facilitates heterochromatin formation in Arabidopsis. Sci. Adv. 9, eadg2699 (2023).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  76. Raskina, O., Shklyar, B. & Nevo, E. The influence of edaphic factors on DNA damage and repair in wild wheat Triticum dicoccoides Körn. (Poaceae, Triticeae). Int. J. Mol. Sci. 24, 6847 (2023).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  77. García-Muse, T. & Aguilera, A. Transcription–replication conflicts: how they occur and how they are resolved. Nat. Rev. Mol. Cell Biol. 17, 553–563 (2016).

    Article  PubMed  Google Scholar 

  78. St Germain, C., Zhao, H. & Barlow, J. H. Transcription–replication collisions—a series of unfortunate events. Biomolecules 11, 1249 (2021).

    Article  Google Scholar 

  79. Bhowmick, R., Mehta, K. P. M., Lerdrup, M. & Cortez, D. Integrator facilitates RNAPII removal to prevent transcription–replication collisions and genome instability. Mol. Cell 83, 2357–2366.e8 (2023).

    Article  CAS  PubMed  Google Scholar 

  80. Pommier, Y., Nussenzweig, A., Takeda, S. & Austin, C. Human topoisomerases and their roles in genome stability and organization. Nat. Rev. Mol. Cell Biol. 23, 407–427 (2022).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  81. Whittaker, C. & Dean, C. The FLC locus: a platform for discoveries in epigenetics and adaptation. Annu. Rev. Cell Dev. Biol. 33, 555–575 (2017).

    Article  CAS  PubMed  Google Scholar 

  82. Rosa, S., Duncan, S. & Dean, C. Mutually exclusive sense–antisense transcription at FLC facilitates environmentally induced gene repression. Nat. Commun. 7, 13031 (2016).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  83. Fang, X. et al. The 3′ processing of antisense RNAs physically links to chromatin-based transcriptional control. Proc. Natl Acad. Sci. USA 117, 15316–15321 (2020).

    Article  PubMed  PubMed Central  Google Scholar 

  84. Xu, C. et al. R-loop resolution promotes co-transcriptional chromatin silencing. Nat. Commun. 12, 1790 (2021).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  85. Inagaki, S., Takahashi, M., Takashima, K., Oya, S. & Kakutani, T. Chromatin-based mechanisms to coordinate convergent overlapping transcription. Nat. Plants 7, 295–302 (2021).

    Article  CAS  PubMed  Google Scholar 

  86. Anindya, R. Single-stranded DNA damage: protecting the single-stranded DNA from chemical attack. DNA Repair (Amst.) 87, 102804 (2020).

    Article  CAS  PubMed  Google Scholar 

  87. Baxter, C. L., Šviković, S., Sale, J. E., Dean, C. & Costa, S. The intersection of DNA replication with antisense 3′ RNA processing in Arabidopsis FLC chromatin silencing. Proc. Natl Acad. Sci. USA 118, e2107483118 (2021).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  88. Sequeira-Mendes, J. et al. Differences in firing efficiency, chromatin, and transcription underlie the developmental plasticity of the Arabidopsis DNA replication origins. Genome Res. 29, 784–797 (2019).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  89. Borg, M. & Berger, F. Chromatin remodelling during male gametophyte development. Plant J. 83, 177–188 (2015).

    Article  CAS  PubMed  Google Scholar 

  90. van Zanten, M. et al. Seed maturation in Arabidopsis thaliana is characterized by nuclear size reduction and increased chromatin condensation. Proc. Natl Acad. Sci. USA 108, 20219–20224 (2011).

    Article  PubMed  PubMed Central  Google Scholar 

  91. Rathke, C., Baarends, W. M., Awe, S. & Renkawitz-Pohl, R. Chromatin dynamics during spermiogenesis. Biochim. Biophys. Acta Gene Regul. Mech. 1839, 155–168 (2014).

    Article  CAS  Google Scholar 

  92. Buttress, T. et al. Histone H2B.8 compacts flowering plant sperm through chromatin phase separation. Nature 611, 614–622 (2022).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  93. Layat, E. et al. The histone chaperone HIRA is a positive regulator of seed germination. Int. J. Mol. Sci. 22, 4031 (2021).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  94. Falk, M., Lukásová, E. & Kozubek, S. Chromatin structure influences the sensitivity of DNA to gamma-radiation. Biochim. Biophys. Acta 1783, 2398–2414 (2008).

    Article  CAS  PubMed  Google Scholar 

  95. Takata, H. et al. Chromatin compaction protects genomic DNA from radiation damage. PLoS ONE 8, e75622 (2013).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  96. Smerdon, M. J., Wyrick, J. J. & Delaney, S. A half century of exploring DNA excision repair in chromatin. J. Biol. Chem. 299, 105118 (2023).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  97. Rocha, L. C., Mittelmann, A., Houben, A. & Techio, V. H. Fragile sites of 45S rDNA of Lolium multiflorum are not hotspots for chromosomal breakages induced by X-ray. Mol. Biol. Rep. 43, 659–665 (2016).

    Article  CAS  PubMed  Google Scholar 

  98. Liu, Q. et al. The histone methyltransferase SUVR2 promotes DSB repair via chromatin remodeling and liquid–liquid phase separation. Mol. Plant 15, 1157–1175 (2022).

    Article  CAS  PubMed  Google Scholar 

  99. Hasegawa, J. et al. Auxin decreases chromatin accessibility through the TIR1/AFBs auxin signaling pathway in proliferative cells. Sci. Rep. 8, 7773 (2018).

    Article  PubMed  PubMed Central  Google Scholar 

  100. Joly, V. & Jacob, Y. Mitotic inheritance of genetic and epigenetic information via the histone H3.1 variant. Curr. Opin. Plant Biol. 75, 102401 (2023).

    Article  CAS  PubMed  Google Scholar 

  101. Jamge, B. et al. Histone variants shape chromatin states in Arabidopsis. eLife 12, RP87714 (2023).

    Article  PubMed  PubMed Central  Google Scholar 

  102. Gao, J. et al. NAP1 family histone chaperones are required for somatic homologous recombination in Arabidopsis. Plant Cell 24, 1437–1447 (2012).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  103. Kolářová, K. et al. Disruption of NAP1 genes in Arabidopsis thaliana suppresses the fas1 mutant phenotype, enhances genome stability and changes chromatin compaction. Plant J. 106, 56–73 (2021).

    Article  PubMed  Google Scholar 

  104. Monroe, J. G. et al. Mutation bias reflects natural selection in Arabidopsis thaliana. Nature 602, 101–105 (2022).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  105. Staunton, P. M., Peters, A. J. & Seoighe, C. Somatic mutations inferred from RNA-seq data highlight the contribution of replication timing to mutation rate variation in a model plant. Genetics 225, iyad128 (2023).

    Article  PubMed  PubMed Central  Google Scholar 

  106. Quiroz, D., Lensink, M., Kliebenstein, D. J. & Monroe, J. G. Causes of mutation rate variability in plant genomes. Annu. Rev. Plant Biol. 74, 751–775 (2023).

    Article  CAS  PubMed  Google Scholar 

  107. Yan, W., Deng, X. W., Yang, C. & Tang, X. The genome-wide EMS mutagenesis bias correlates with sequence context and chromatin structure in rice. Front. Plant Sci. 12, 579675 (2021).

    Article  PubMed  PubMed Central  Google Scholar 

  108. Sabarinathan, R., Mularoni, L., Deu-Pons, J., Gonzalez-Perez, A. & López-Bigas, N. Nucleotide excision repair is impaired by binding of transcription factors to DNA. Nature 532, 264–267 (2016).

    Article  CAS  PubMed  Google Scholar 

  109. Henry, I. M. et al. Efficient genome-wide detection and cataloging of EMS-induced mutations using exome capture and next-generation sequencing. Plant Cell 26, 1382–1397 (2014).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  110. Krasileva, K. V. et al. Uncovering hidden variation in polyploid wheat. Proc. Natl Acad. Sci. USA 114, E913–E921 (2017).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  111. Belfield, E. J. et al. DNA mismatch repair preferentially protects genes from mutation. Genome Res. 28, 66–74 (2018).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  112. Quiroz, D. et al. The H3K4me1 histone mark recruits DNA repair to functionally constrained genomic regions in plants. Preprint at bioRxiv https://doi.org/10.1101/2022.05.28.493846 (2022).

  113. Lai, J. et al. The transcriptional coactivator ADA2b recruits a structural maintenance protein to double-strand breaks during DNA repair in plants. Plant Physiol. 176, 2613–2622 (2018).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  114. Jiang, J. et al. A diRNA–protein scaffold module mediates SMC5/6 recruitment in plant DNA repair. Plant Cell 34, 3899–3914 (2022).

    Article  PubMed  PubMed Central  Google Scholar 

  115. Jacob, Y. et al. Regulation of heterochromatic DNA replication by histone H3 lysine 27 methyltransferases. Nature 466, 987–991 (2010).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  116. Feng, W. et al. Large-scale heterochromatin remodeling linked to overreplication-associated DNA damage. Proc. Natl Acad. Sci. USA 114, 406–411 (2017).

    Article  CAS  PubMed  Google Scholar 

  117. Davarinejad, H. et al. The histone H3.1 variant regulates TONSOKU-mediated DNA repair during replication. Science 375, 1281–1286 (2022).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  118. Molinier, J., Lechner, E., Dumbliauskas, E. & Genschik, P. Regulation and role of Arabidopsis CUL4–DDB1A–DDB2 in maintaining genome integrity upon UV stress. PLoS Genet. 4, e1000093 (2008).

    Article  PubMed  PubMed Central  Google Scholar 

  119. Schalk, C. et al. DNA DAMAGE BINDING PROTEIN2 shapes the DNA methylation landscape. Plant Cell 28, 2043–2059 (2016).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  120. Córdoba-Cañero, D., Cognat, V., Ariza, R. R., Roldán Arjona, T. & Molinier, J. Dual control of ROS1-mediated active DNA demethylation by DNA damage-binding protein 2 (DDB2). Plant J. 92, 1170–1181 (2017).

    Article  PubMed  Google Scholar 

  121. Kinner, A., Wu, W., Staudt, C. & Iliakis, G. H2AX in recognition and signaling of DNA double-strand breaks in the context of chromatin. Nucleic Acids Res. 36, 5678–5694 (2008).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  122. Friesner, J. D., Liu, B., Culligan, K. & Britt, A. B. Ionizing radiation-dependent gamma-H2AX focus formation requires ataxia telangiectasia mutated and ataxia telangiectasia mutated and Rad3-related. Mol. Biol. Cell 16, 2566–2576 (2005).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  123. Bourguet, P. et al. The histone variant H2A.W and linker histone H1 co-regulate heterochromatin accessibility and DNA methylation. Nat. Commun. 12, 2683 (2021).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  124. Puizina, J., Siroky, J., Mokros, P., Schweizer, D. & Riha, K. Mre11 deficiency in Arabidopsis is associated with chromosomal instability in somatic cells and Spo11-dependent genome fragmentation during meiosis. Plant Cell 16, 1968–1978 (2004).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  125. Waterworth, W. M. et al. NBS1 is involved in DNA repair and plays a synergistic role with ATM in mediating meiotic homologous recombination in plants. Plant J. 52, 41–52 (2007).

    Article  CAS  PubMed  Google Scholar 

  126. Amiard, S. et al. Distinct roles of the ATR kinase and the Mre11–Rad50–Nbs1 complex in the maintenance of chromosomal stability in Arabidopsis. Plant Cell 22, 3020–3033 (2010).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  127. Fan, T. et al. Arabidopsis γ-H2A.X-INTERACTING PROTEIN participates in DNA damage response and safeguards chromatin stability. Nat. Commun. 13, 7942 (2022).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  128. Lorković, Z. J., Klingenbrunner, M., Cho, C. H. & Berger, F. Identification of plants' functional counterpart of the metazoan mediator of DNA Damage checkpoint 1. EMBO Rep. 25, 1936–1961 (2024).

    Article  PubMed  PubMed Central  Google Scholar 

  129. Arnould, C. et al. Loop extrusion as a mechanism for formation of DNA damage repair foci. Nature 590, 660–665 (2021).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  130. Huang, Y. et al. The matrix revolutions: towards the decoding of the plant chromatin three-dimensional reality. J. Exp. Bot. 71, 5129–5147 (2020).

    Article  CAS  PubMed  Google Scholar 

  131. Liu, C., Cheng, Y.-J., Wang, J.-W. & Weigel, D. Prominent topologically associated domains differentiate global chromatin packing in rice from Arabidopsis. Nat. Plants 3, 742–748 (2017).

    Article  CAS  PubMed  Google Scholar 

  132. Frigerio, C. et al. The chromatin landscape around DNA double-strand breaks in yeast and its influence on DNA repair pathway choice. Int. J. Mol. Sci. 24, 3248 (2023).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  133. Hirakawa, T. et al. LSD1–LIKE1-mediated H3K4me2 demethylation is required for homologous recombination repair. Plant Physiol. 181, 499–509 (2019).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  134. Li, C., Guo, Y., Wang, L. & Yan, S. The SMC5/6 complex recruits the PAF1 complex to facilitate DNA double-strand break repair in Arabidopsis. EMBO J. 42, e112756 (2023).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  135. Roitinger, E. et al. Quantitative phosphoproteomics of the ataxia telangiectasia-mutated (ATM) and ataxia telangiectasia-mutated and rad3-related (ATR) dependent DNA damage response in Arabidopsis thaliana. Mol. Cell. Proteom. 14, 556–571 (2015).

    Article  CAS  Google Scholar 

  136. Donà, M. & Mittelsten Scheid, O. DNA damage repair in the context of plant chromatin. Plant Physiol. 168, 1206–1218 (2015).

    Article  PubMed  PubMed Central  Google Scholar 

  137. Campi, M., D’Andrea, L., Emiliani, J. & Casati, P. Participation of chromatin-remodeling proteins in the repair of ultraviolet-B-damaged DNA. Plant Physiol. 158, 981–995 (2012).

    Article  CAS  PubMed  Google Scholar 

  138. Aleksandrov, R., Hristova, R., Stoynov, S. & Gospodinov, A. The chromatin response to double-strand DNA breaks and their repair. Cells 9, 1853 (2020).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  139. Banerjee, S. & Roy, S. An insight into understanding the coupling between homologous recombination mediated DNA repair and chromatin remodeling mechanisms in plant genome: an update. Cell Cycle 20, 1760–1784 (2021).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  140. Shaked, H., Avivi-Ragolsky, N. & Levy, A. A. Involvement of the Arabidopsis SWI2/SNF2 chromatin remodeling gene family in DNA damage response and recombination. Genetics 173, 985–994 (2006).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  141. Jiang, J. et al. A SWI/SNF subunit regulates chromosomal dissociation of structural maintenance complex 5 during DNA repair in plant cells. Proc. Natl Acad. Sci. USA 116, 15288–15296 (2019).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  142. Wu, N. & Yu, H. The Smc complexes in DNA damage response. Cell Biosci. 2, 5 (2012).

    Article  PubMed  PubMed Central  Google Scholar 

  143. Bansbach, C. E., Bétous, R., Lovejoy, C. A., Glick, G. G. & Cortez, D. The annealing helicase SMARCAL1 maintains genome integrity at stalled replication forks. Genes Dev. 23, 2405–2414 (2009).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  144. Zhang, Y. et al. CHR721, interacting with OsRPA1a, is essential for both male and female reproductive development in rice. Plant Mol. Biol. 103, 473–487 (2020).

    Article  CAS  PubMed  Google Scholar 

  145. Zhang, Y., Chen, Q., Zhu, G., Zhang, D. & Liang, W. Chromatin-remodeling factor CHR721 with non-canonical PIP-box interacts with OsPCNA in rice. BMC Plant Biol. 22, 164 (2022).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  146. Lugli, N., Sotiriou, S. K. & Halazonetis, T. D. The role of SMARCAL1 in replication fork stability and telomere maintenance. DNA Repair (Amst.) 56, 129–134 (2017).

    Article  CAS  PubMed  Google Scholar 

  147. Mazin, A. V., Mazina, O. M., Bugreev, D. V. & Rossi, M. J. Rad54, the motor of homologous recombination. DNA Repair (Amst.) 9, 286–302 (2010).

    Article  CAS  PubMed  Google Scholar 

  148. Ceballos, S. J. & Heyer, W.-D. Functions of the Snf2/Swi2 family Rad54 motor protein in homologous recombination. Biochim. Biophys. Acta 1809, 509–523 (2011).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  149. Hirakawa, T., Hasegawa, J., White, C. I. & Matsunaga, S. RAD54 forms DNA repair foci in response to DNA damage in living plant cells. Plant J. 90, 372–382 (2017).

    Article  CAS  PubMed  Google Scholar 

  150. Hirakawa, T. & Matsunaga, S. Characterization of DNA repair foci in root cells of Arabidopsis in response to DNA damage. Front. Plant Sci. 10, 990 (2019).

    Article  PubMed  PubMed Central  Google Scholar 

  151. Hirakawa, T., Katagiri, Y., Ando, T. & Matsunaga, S. DNA double-strand breaks alter the spatial arrangement of homologous loci in plant cells. Sci. Rep. 5, 11058 (2015).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  152. Meschichi, A. et al. The plant-specific DDR factor SOG1 increases chromatin mobility in response to DNA damage. EMBO Rep. 23, e54736 (2022).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  153. Zhang, C. et al. The chromatin-remodeling factor AtINO80 plays crucial roles in genome stability maintenance and in plant development. Plant J. 82, 655–668 (2015).

    Article  CAS  PubMed  Google Scholar 

  154. Kandasamy, M. K., McKinney, E. C., Deal, R. B., Smith, A. P. & Meagher, R. B. Arabidopsis actin-related protein ARP5 in multicellular development and DNA repair. Dev. Biol. 335, 22–32 (2009).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  155. Zhou, W. et al. Distinct roles of the histone chaperones NAP1 and NRP and the chromatin-remodeling factor INO80 in somatic homologous recombination in Arabidopsis thaliana. Plant J. 88, 397–410 (2016).

    Article  CAS  PubMed  Google Scholar 

  156. Rosa, M., Von Harder, M., Cigliano, R. A., Schlögelhofer, P. & Mittelsten Scheid, O. The Arabidopsis SWR1 chromatin-remodeling complex is important for DNA repair, somatic recombination, and meiosis. Plant Cell 25, 1990–2001 (2013).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  157. Zhang, J. et al. The SUMO ligase MMS21 profoundly influences maize development through its impact on genome activity and stability. PLoS Genet. 17, e1009830 (2021).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  158. Xu, P. et al. AtMMS21, an SMC5/6 complex subunit, is involved in stem cell niche maintenance and DNA damage responses in Arabidopsis roots. Plant Physiol. 161, 1755–1768 (2013).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  159. Oztas, O., Selby, C. P., Sancar, A. & Adebali, O. Genome-wide excision repair in Arabidopsis is coupled to transcription and reflects circadian gene expression patterns. Nat. Commun. 9, 1503 (2018).

    Article  PubMed  PubMed Central  Google Scholar 

  160. Selby, C. P., Lindsey-Boltz, L. A., Li, W. & Sancar, A. Molecular mechanisms of transcription-coupled repair. Annu. Rev. Biochem. 92, 115–144 (2023).

    Article  CAS  PubMed  Google Scholar 

  161. Zhang, C. et al. Arabidopsis cockayne syndrome A-like proteins 1A and 1B form a complex with CULLIN4 and damage DNA binding protein 1A and regulate the response to UV irradiation. Plant Cell 22, 2353–2369 (2010).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  162. Kaya, S., Adebali, O., Oztas, O. & Sancar, A. Genome-wide excision repair map of cyclobutane pyrimidine dimers in Arabidopsis and the roles of CSA1 and CSA2 proteins in transcription-coupled repair. Photochem. Photobiol. 98, 707–712 (2022).

    Article  CAS  PubMed  Google Scholar 

  163. Al Khateeb, W. M., Sher, A. A., Marcus, J. M. & Schroeder, D. F. UVSSA, UBP12, and RDO2/TFIIS contribute to Arabidopsis UV tolerance. Front. Plant Sci. 10, 516 (2019).

    Article  PubMed  PubMed Central  Google Scholar 

  164. Schalk, C. et al. Small RNA-mediated repair of UV-induced DNA lesions by the DNA DAMAGE-BINDING PROTEIN 2 and ARGONAUTE 1. Proc. Natl Acad. Sci. USA 114, E2965–E2974 (2017).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  165. Wei, W. et al. A role for small RNAs in DNA double-strand break repair. Cell 149, 101–112 (2012).

    Article  CAS  PubMed  Google Scholar 

  166. Miki, D. et al. Efficient generation of diRNAs requires components in the posttranscriptional gene silencing pathway. Sci. Rep. 7, 301 (2017).

    Article  PubMed  PubMed Central  Google Scholar 

  167. Wang, Q. & Goldstein, M. Small RNAs recruit chromatin-modifying enzymes MMSET and Tip60 to reconfigure damaged DNA upon double-strand break and facilitate repair. Cancer Res. 76, 1904–1915 (2016).

    Article  CAS  PubMed  Google Scholar 

  168. Durut, N. et al. Long noncoding RNAs contribute to DNA damage resistance in Arabidopsis thaliana. Genetics 225, iyad135 (2023).

    Article  PubMed  PubMed Central  Google Scholar 

  169. Herbst, J., Nagy, S. H., Vercauteren, I., De Veylder, L. & Kunze, R. The long non-coding RNA LINDA restrains cellular collapse following DNA damage in Arabidopsis thaliana. Plant J. 116, 1370–1384 (2023).

    Article  CAS  PubMed  Google Scholar 

  170. Durut, N. & Mittelsten Scheid, O. The role of noncoding RNAs in double-strand break repair. Front. Plant Sci. 10, 1155 (2019).

    Article  PubMed  PubMed Central  Google Scholar 

  171. Bourguet, P. et al. DNA polymerase epsilon is required for heterochromatin maintenance in Arabidopsis. Genome Biol. 21, 283 (2020).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  172. Roldán-Arjona, T., Ariza, R. R. & Córdoba-Cañero, D. DNA base excision repair in plants: an unfolding story with familiar and novel characters. Front. Plant Sci. 10, 1055 (2019).

    Article  PubMed  PubMed Central  Google Scholar 

  173. Martínez-Macías, M. I., Córdoba-Cañero, D., Ariza, R. R. & Roldán-Arjona, T. The DNA repair protein XRCC1 functions in the plant DNA demethylation pathway by stimulating cytosine methylation (5-meC) excision, gap tailoring, and DNA ligation. J. Biol. Chem. 288, 5496–5505 (2013).

    Article  PubMed  PubMed Central  Google Scholar 

  174. Córdoba-Cañero, D., Morales-Ruiz, T., Roldán-Arjona, T. & Ariza, R. R. Single-nucleotide and long-patch base excision repair of DNA damage in plants. Plant J. 60, 716–728 (2009).

    Article  PubMed  PubMed Central  Google Scholar 

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Acknowledgements

We apologize to authors whose work is related to plant chromatin dynamics and RNA metabolism involved in DNA damage or genome integrity maintenance but could not be cited because of either our oversight or space limitation. This work was supported by a PhD fellowship from the University Paris-Saclay to C.B.-S. and a research grant from Agence Nationale de la Recherche (no. ANR-CE20-0027) to C.R.

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Authors and Affiliations

  1. Université Paris-Saclay, CNRS, INRAE, Université d’Evry, Institute of Plant Sciences Paris-Saclay, Orsay, France

    Clara Bergis-Ser, Meega Reji, David Latrasse, Catherine Bergounioux, Moussa Benhamed & Cécile Raynaud

  2. Indian Institute of Science Education and Research Thiruvananthapuram, Vithura, India

    Meega Reji

  3. Université Paris Cité, Institute of Plant Sciences Paris-Saclay, Gif-sur-Yvette, France

    Moussa Benhamed

  4. Institut Universitaire de France, Orsay, France

    Moussa Benhamed

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  1. Clara Bergis-Ser
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C.R. and C.B.-S. conceptualized the manuscript framework. C.R., C.B.-S. and M.R. wrote the original draft of the manuscript. C.B.-S., C.R. and M.B. produced, reviewed and edited the figures. M.B., D.L. and C.B. reviewed the manuscript. C.B.-S. and C.R. edited the manuscript.

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Correspondence to Cécile Raynaud.

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Bergis-Ser, C., Reji, M., Latrasse, D. et al. Chromatin dynamics and RNA metabolism are double-edged swords for the maintenance of plant genome integrity. Nat. Plants (2024). https://doi.org/10.1038/s41477-024-01678-z

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