Journal ArticleDOI
Mechanism of replication fork reversal and protection by human RAD51 and RAD51 paralogs
Petr Cejka,Swagata Halder,Aurore Sanchez,Lepakshi Ranjha,Angelo Taglialatela,Giordano Reginato,Ilaria Ceppi,Ananya Acharya,Roopesh Anand,Alberto Ciccia +9 more
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TLDR
It is shown that the protective function of RAD51 unexpectedly depends on its binding to double-stranded DNA, and higher RAD51 concentrations are required for DNA protection compared to reversal, and the mechanisms of the non-canonical functions of RAD 51 and paralogs in replication fork reversal and protection are defined.Abstract:
RAD51 functions in DNA double-strand break repair by homologous recombination, and by a yet undefined mechanism in the metabolism of challenged replication forks. Here we show that RAD51 directly and specifically promotes the strand annealing and branch migration activities of SMARCAL1 and ZRANB3 but not HLTF, stimulating thus fork reversal. We also find that the RAD51 paralog complex, RAD51B-RAD51C-RAD51D-XRCC2 (BCDX2), additionally stimulates SMARCAL1 and ZRANB3 in fork remodeling. DNA binding by RAD51 is required, and the interplay of RAD51, paralogs and the fork remodelers involves direct physical interactions. Upon reversal, RAD51 protects replication forks from degradation by MRE11, DNA2 and EXO1 nucleases. We show that the protective function of RAD51 unexpectedly depends on its binding to double-stranded DNA, and higher RAD51 concentrations are required for DNA protection compared to reversal. Together, we define the mechanisms of the non-canonical functions of RAD51 and paralogs in replication fork reversal and protection.read more
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After the bill, what next?
TL;DR: Last week the BMJ and Nuffield Trust brought together some of the leading voices in healthcare to consider what life in the NHS will be like after the Health and Social Care Bill passes into legislation.
Peer ReviewDOI
Author response: Concerted action of the MutLβ heterodimer and Mer3 helicase regulates the global extent of meiotic gene conversion
Yann Duroc,Yann Duroc,Rajeev Kumar,Rajeev Kumar,Lepakshi Ranjha,Céline Adam,Céline Adam,Raphael Guerois,Khan Md Muntaz,Marie-Claude Marsolier-Kergoat,Marie-Claude Marsolier-Kergoat,Florent Dingli,Raphaelle Laureau,Raphaelle Laureau,Damarys Loew,Bertrand Llorente,Jean-Baptiste Charbonnier,Petr Cejka,Valérie Borde,Valérie Borde +19 more
Histone Methylation by SETD1A Protects Nascent DNA through the Nucleosome Chaperone Activity of FANCD2
Martin R. Higgs,Koichi Sato,John J. Reynolds,Shabana Begum,Rachel Bayley,Amalia Goula,Audrey Vernet,Karissa L. Paquin,David G. Skalnik,Wataru Kobayashi,Minoru Takata,Niall G. Howlett,Hitoshi Kurumizaka,Hiroshi Kimura,Grant S. Stewart +14 more
TL;DR: The ability of SETD1A to prevent degradation of these structures is mediated by its ability to catalyze methylation on Lys4 of histone H3 (H3K4) at replication forks, which enhances FANCD2dependent histone chaperone activity as mentioned in this paper.
References
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Journal ArticleDOI
The SIOD disorder protein SMARCAL1 is an RPA-interacting protein involved in replication fork restart
Alberto Ciccia,Andrea L. Bredemeyer,Mathew E. Sowa,Marie-Emilie Terret,Prasad V. Jallepalli,J. Wade Harper,Stephen J. Elledge +6 more
TL;DR: It is demonstrated that SMARCAL1 directly interacts with Replication protein A (RPA) and is recruited to sites of DNA damage in an RPA-dependent manner, which indicates that the symptoms of SIOD may be caused, at least in part, by defects in the cellular response to DNA replication stress.
Journal ArticleDOI
Rad51 paralogues Rad55-Rad57 balance the antirecombinase Srs2 in Rad51 filament formation.
Jie Liu,Ludovic Renault,Xavier Veaute,Francis Fabre,Henning Stahlberg,Henning Stahlberg,Wolf Dietrich Heyer +6 more
TL;DR: It is proposed that the Rad51 presynaptic filament is a meta-stable reversible intermediate, whose assembly and disassembly is governed by the balance between Rad55–Rad57 and Srs2, providing a key regulatory mechanism controlling the initiation of homologous recombination.
Journal Article
Main steps in DNA double-strand break repair
TL;DR: The main pathways of eukaryotic DNA double-strand break repair are reviewed with the focus on homologous recombination and its various sub paths, including non-homologous end- joining and microhomology-mediated end-joining and insights into how these pathways are regulated are offered.
Journal ArticleDOI
Replication Fork Slowing and Reversal upon DNA Damage Require PCNA Polyubiquitination and ZRANB3 DNA Translocase Activity.
Marko Vujanovic,Jana Krietsch,Maria Chiara Raso,Nastassja Terraneo,Ralph Zellweger,Jonas A. Schmid,Angelo Taglialatela,Jen-Wei Huang,Cory L. Holland,Katharina Zwicky,Raquel Herrador,Heinz Jacobs,David Cortez,Alberto Ciccia,Lorenza Penengo,Massimo Lopes +15 more
TL;DR: It is shown that damage-induced fork reversal in mammalian cells requires PCNA ubiquitination, UBC13, and K63-linked polyubiquitin chains, previously involved in error-free damage tolerance, and targeting these fork protection systems represents a promising strategy to potentiate cancer chemotherapy.
Journal ArticleDOI
HARP is an ATP-driven annealing helicase.
Timur Yusufzai,James T. Kadonaga +1 more
TL;DR: It is found that HARP is an ATP-dependent annealing helicase that rewinds single-stranded DNA bubbles that are stably bound by replication protein A that acts throughout the genome to oppose the action of DNA-unwinding activities in the nucleus.
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Rad51-Independent Interchromosomal Double-Strand Break Repair by Gene Conversion Requires Rad52 but Not Rad55, Rad57, or Dmc1
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