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
Isomerization of BRCA1–BARD1 promotes replication fork protection
Manuel Daza-Martin,Manuel Daza-Martin,Katarzyna Starowicz,Mohammed Jamshad,Stephanie Tye,George E. Ronson,Hannah L. Mackay,Anoop Singh Chauhan,Alexandra K. Walker,Helen R Stone,James F.J. Beesley,Jennifer L. Coles,Jennifer L. Coles,Alexander J Garvin,Grant S. Stewart,Thomas J. McCorvie,Xiaodong Zhang,Ruth M Densham,Joanna R. Morris +18 more
TL;DR: It is shown that BRCA1 in complex with BARD1, and not the canonical BRC a1–PALB2 interaction, is required for fork protection, and a BRCa1-mediated pathway that governs replication fork protection is revealed.
Journal ArticleDOI
Non-enzymatic roles of human RAD51 at stalled replication forks
TL;DR: It is found that cells lacking RAD51’s enzymatic activity protect replication forks from MRE11-dependent degradation, as expected from previous studies, and it is unexpected that RAD51's strand exchange activity is not required to convert stalled forks to a form that can be degraded by DNA2.
Journal ArticleDOI
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: It is reported that histone methylation by the lysine methyltransferase SETD1A is crucial for protecting stalled replication forks from deleterious resection.
Journal ArticleDOI
Human DNA helicase HELQ participates in DNA interstrand crosslink tolerance with ATR and RAD51 paralogs
TL;DR: Results indicate that HELQ operates in an arm of DNA repair and signalling in response to ICL, and the association with RAD51 paralogs suggests HELQ as a candidate ovarian cancer gene.
Journal ArticleDOI
FIGNL1-containing protein complex is required for efficient homologous recombination repair
Jingsong Yuan,Junjie Chen +1 more
TL;DR: This study uncovers a protein complex, which consists of FIGNL1 and KIAA0146/SPIDR, in DNA repair and provides potential directions for cancer diagnosis and therapy.
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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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