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A study reports that CRISPR–Cas9 induces extensive on-target mutagenesis in mouse and human cells, calling for greater caution when using it in clinical contexts.
Poly(dA:dT) tracts characterize strong DNA replication origins in mammals and cause replication-fork collapse and DNA breaks that underlie the expression of fragile sites.
A new study in Nature identifies a molecular axis linking diabetes to cancer, whereby AMPK, which is inhibited in high glucose conditions, regulates the stability of TET2 DNA demethylase, thereby impacting DNA methylation and gene expression.
Rebecca Taylor discusses the elegance and importance of early discoveries from the Walter laboratory on the unfolded protein response, and why they have become landmark studies.
G protein coupled receptors (GPCRs) transmit a variety of signals, mostly by engaging G proteins, but G protein-independent signalling through arrestins has also been demonstrated. Based on recent experimental evidence, Gutkind and Kostenis argue that arrestins serve as important signal modulators instead of as independent signal transducers.
Senescent cells secrete a multitude of factors that modulate their local environment — a phenomenon known as senescence-associated secretory phenotype (SASP). David Bernard highlights that the SASP secretome can be flexibly regulated, resulting in different types of SASP, which contributes to the versatility of responses triggered by senescent cells.
Many eukaryotic proteins, including key transcription regulators, contain intrinsically disordered regions (IDRs), which serve as flexible interaction platforms. The molecular understanding of IDR-based interactions is now emerging, providing new insights into how IDRs promote protein compartmentalization and/or phase separation and how these processes regulate gene expression.
Two independent studies now show that polymerization of branched actin at DNA double-strand breaks (DSBs) mediates chromatin dynamics associated with homology-directed repair and is required for a robust and error-free DSB repair process.
MicroRNAs derived from a virus and teratocytes of a parasitic wasp are expressed in a host moth and delay its development by inhibiting the ecdysone receptor.
Increased shortening of RNA 3′ untranslated regions associated with tumorigenic transformation interferes with competing endogenous RNA (ceRNA) networks, which results in trans-repression of tumour suppressors through microRNA-mediated silencing.
Biomolecules can phase separate and form condensates that have roles in diverse cellular processes and contexts. Michnick and Bergeron-Sandoval comment on this rapidly progressing field and envisage that the study of biological phase separation will bring new understanding of cell and developmental biology.
The spindle checkpoint complex BUB3–BUB1 facilitates telomere replication through recruitment of the helicase BLM, and the telomere capping protein TRF2 promotes replication at pericentromeres by recruiting the helicase RTEL1; both helicases resolve G-quadruplex structures.
Cellular organelles extensively communicate with each other by close interactions, known as membrane contact sites. Schuldiner and Bohnert comment on the progress of this rapidly developing field, highlighting that the complexity of interactions at membrane contact sites is only now starting to emerge.
Kikuë Tachibana discusses some of the key findings of the seminal works of Sir John Gurdon on nuclear reprogramming and how, by being examples of scientific rigour, they have inspired her own research.