Nature, Journal Year: 2024, Volume and Issue: 632(8023), P. 166 - 173
Published: July 17, 2024
Language: Английский
Journal of Biological Chemistry, Journal Year: 2023, Volume and Issue: 299(6), P. 104800 - 104800
Published: May 9, 2023
For cells, it is important to repair DNA damage, such as double-strand and single-strand breaks, because unrepaired can compromise genetic integrity, potentially leading cell death or cancer. Cells have multiple damage pathways that been the subject of detailed genetic, biochemical, structural studies. Recently, scientific community has started gain evidence breaks may occur within biomolecular condensates also contribute through concentrating genotoxic agents used treat various cancers. Here, we summarize key features note where they implicated in breaks. We describe suggesting be involved other types including nucleotide modifications (e.g., mismatch oxidized bases), bulky lesions, among others. Finally, discuss old new mysteries could now addressed considering properties condensates, chemoresistance mechanisms. Chemical changes highly harmful living organisms. DNA, like molecules, undergo chemical reactions. 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Language: Английский
Citations
28
bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2024, Volume and Issue: unknown
Published: June 3, 2024
ABSTRACT Intrinsically disordered regions (IDRs) are critical for a wide variety of cellular functions, many which involve interactions with partner proteins. Molecular recognition is typically considered through the lens sequence-specific binding events. However, growing body work has shown that IDRs often interact partners in manner does not depend on precise order amino acid order, instead driven by complementary chemical leading to bound-state complexes. Despite this emerging paradigm, we lack tools describe, quantify, predict, and interpret these types structurally heterogeneous from underlying sequences. Here, repurpose physics developed originally molecular simulations develop an approach predicting intermolecular between Our enables direct prediction phase diagrams, identification chemically-specific interaction hotspots IDRs, route test mechanistic hypotheses regarding IDR function context recognition. We use our examine range systems questions highlight its versatility applicability.
Language: Английский
Citations
16
Nature Cell Biology, Journal Year: 2024, Volume and Issue: 26(8), P. 1309 - 1321
Published: July 5, 2024
Abstract Transcription factors (TFs) control specificity and activity of gene transcription, but whether a relationship between these two features exists is unclear. Here we provide evidence for an evolutionary trade-off the in human TFs encoded as submaximal dispersion aromatic residues their intrinsically disordered protein regions. We identified approximately 500 that encode short periodic blocks regions, resembling imperfect prion-like sequences. Mutation reduced transcriptional activity, whereas increasing multiple enhanced reprogramming efficiency, promoted liquid–liquid phase separation vitro more promiscuous DNA binding cells. Together with recent work on enhancer elements, results suggest important role suboptimal control. propose rational engineering amino acid alter may be strategy to optimize TF-dependent processes, including cellular reprogramming.
Language: Английский
Citations
16
Computers in Biology and Medicine, Journal Year: 2024, Volume and Issue: 176, P. 108620 - 108620
Published: May 15, 2024
Language: Английский
Citations
14
Nature, Journal Year: 2024, Volume and Issue: 632(8023), P. 166 - 173
Published: July 17, 2024
Language: Английский
Citations
14