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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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
Mammalian RAD51 paralogs protect nascent DNA at stalled forks and mediate replication restart
TL;DR: It is shown that RAD51 paralogs localize to nascent DNA and common fragile sites upon replication fork stalling and prevent degradation of stalled forks and promote the restart of halted replication to avoid replication fork collapse, thereby maintaining genomic integrity and suppressing tumorigenesis.
Journal ArticleDOI
HLTF Promotes Fork Reversal, Limiting Replication Stress Resistance and Preventing Multiple Mechanisms of Unrestrained DNA Synthesis.
Gongshi Bai,Chames Kermi,Henriette Stoy,Carl J. Schiltz,Julien Bacal,Angela M. Zaino,M. Kyle Hadden,Brandt F. Eichman,Massimo Lopes,Karlene A. Cimprich +9 more
TL;DR: It is demonstrated that HLTF-deficient cells fail to undergo fork reversal in vivo and rely on the primase-polymerase PRIMPOL for repriming, unrestrained replication, and S phase progression upon limiting nucleotide levels, suggesting that HL TF promotes fork remodeling, preventing other mechanisms of replication stress tolerance in cancer cells.
Journal ArticleDOI
Physical Interaction of RECQ5 Helicase with RAD51 Facilitates Its Anti-recombinase Activity
Sybille Schwendener,Steven Raynard,Shreya Paliwal,Anita Cheng,Radhakrishnan Kanagaraj,Igor Shevelev,Jeremy M. Stark,Patrick Sung,Pavel Janscak +8 more
TL;DR: Support is provided for the proposal that interaction with RAD51 is critical for the anti-recombinase attribute of RECQ5, a member of the RecQ family of DNA helicases, which mediates the invasion of a homologous DNA molecule.
Journal ArticleDOI
TIMMDC1/C3orf1 Functions as a Membrane-Embedded Mitochondrial Complex I Assembly Factor through Association with the MCIA Complex
TL;DR: A new membrane-embedded CI assembly factor is defined and provided a resource for further analysis of CI biology and Quantitative proteomics demonstrated a role for TIMMDC1 in assembly of membrane- embedded and soluble arms of the complex.
Journal ArticleDOI
RADX Modulates RAD51 Activity to Control Replication Fork Protection.
Kamakoti P. Bhat,Archana Krishnamoorthy,Huzefa Dungrawala,Edwige B. Garcin,Mauro Modesti,David Cortez +5 more
TL;DR: RAD51 promotes homologous recombination repair of double-strand breaks and acts during DNA replication to facilitate fork reversal and protect nascent DNA strands from nuclease digestion, and RADX modulates stalled fork protection by antagonizing RAD51.
Related Papers (5)
Rad51-Independent Interchromosomal Double-Strand Break Repair by Gene Conversion Requires Rad52 but Not Rad55, Rad57, or Dmc1
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