Transcriptionally active chromatin recruits homologous recombination at DNA double-strand breaks
François Aymard,Béatrix Bugler,Christine K. Schmidt,Emmanuelle Guillou,Pierre Caron,Sébastien Briois,Jason S. Iacovoni,Virginie Daburon,Kyle M. Miller,Stephen P. Jackson,Gaëlle Legube +10 more
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TLDR
This study demonstrates a primary role in DSB repair of the chromatin context in which a break occurs and identifies an HR-prone subset of DSBs that recruit the HR protein RAD51, undergo resection and rely on RAD51 for efficient repair.Abstract:
Although both homologous recombination (HR) and nonhomologous end joining can repair DNA double-strand breaks (DSBs), the mechanisms by which one of these pathways is chosen over the other remain unclear. Here we show that transcriptionally active chromatin is preferentially repaired by HR. Using chromatin immunoprecipitation-sequencing (ChIP-seq) to analyze repair of multiple DSBs induced throughout the human genome, we identify an HR-prone subset of DSBs that recruit the HR protein RAD51, undergo resection and rely on RAD51 for efficient repair. These DSBs are located in actively transcribed genes and are targeted to HR repair via the transcription elongation-associated mark trimethylated histone H3 K36. Concordantly, depletion of SETD2, the main H3 K36 trimethyltransferase, severely impedes HR at such DSBs. Our study thereby demonstrates a primary role in DSB repair of the chromatin context in which a break occurs.read more
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DNA double-strand break repair-pathway choice in somatic mammalian cells.
TL;DR: This Review considers DSB repair-pathway choice in somatic mammalian cells as a series of ‘decision trees’, and explores how defective pathway choice can lead to genomic instability.
Journal ArticleDOI
Ribosome biogenesis in cancer: new players and therapeutic avenues
TL;DR: The most recent findings that provide new insights into the molecular basis of ribosome biogenesis in cancer are highlighted and the perspective on how these observations present opportunities for the design of new targeted cancer treatments is offered.
Journal ArticleDOI
SETD2-Dependent Histone H3K36 Trimethylation Is Required for Homologous Recombination Repair and Genome Stability
Sophia X. Pfister,Sara Ahrabi,Lykourgos-Panagiotis Zalmas,Sovan Sarkar,François Aymard,François Aymard,Csanád Z. Bachrati,Thomas Helleday,Gaëlle Legube,Gaëlle Legube,Nicholas B. La Thangue,Andrew C.G. Porter,Timothy C. Humphrey +12 more
TL;DR: A role for H3K36 trimethylation in homologous recombination (HR) repair in human cells is defined and it is proposed that error-free HR repair within H3k36me3-decorated transcriptionally active genomic regions promotes cell homeostasis.
Journal ArticleDOI
Regulation of Single-Strand Annealing and its Role in Genome Maintenance
TL;DR: The mechanism of SSA and its regulation is described, including the cellular conditions that may favor SSA versus other DSB repair events, and the potential contribution of Ssa to cancer-associated genome rearrangements, and to DSB-induced gene targeting.
Journal ArticleDOI
R Loops: From Physiological to Pathological Roles
TL;DR: Given the R-loop impact on chromatin and genome organization and its potential relation with genetic diseases, this work reviews R- loop homeostasis as well as their physiological and pathological roles.
References
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53BP1 Inhibits Homologous Recombination in Brca1-Deficient Cells by Blocking Resection of DNA Breaks
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A User's Guide to the Encyclopedia of DNA Elements (ENCODE)
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TL;DR: An overview of the project and the resources it is generating and the application of ENCODE data to interpret the human genome are provided.
Journal ArticleDOI
An auxin-based degron system for the rapid depletion of proteins in nonplant cells
TL;DR: The auxin-inducible degron (AID) system allowed rapid and reversible degradation of target proteins in response to auxin and enabled us to generate efficient conditional mutants of essential proteins in yeast as well as cell lines derived from chicken, mouse, hamster, monkey and human cells, thus offering a powerful tool to control protein expression and study protein function.