Rad51 Paralogs Remodel Pre-synaptic Rad51 Filaments to Stimulate Homologous Recombination.

doi:10.1016/J.CELL.2015.06.015

Home
/
Papers
/
Rad51 Paralogs Remodel Pre-synaptic Rad51 Filaments to Stimulate Homologous Recombination.

Journal Article•DOI•

Rad51 Paralogs Remodel Pre-synaptic Rad51 Filaments to Stimulate Homologous Recombination.

Martin R.G. Taylor¹, Mário Špírek², Kathy R. Chaurasiya³, Jordan D. Ward¹, Jordan D. Ward⁴, Raffaella Carzaniga¹, Xiong Yu⁵, Edward H. Egelman⁵, Lucy M. Collinson¹, David Rueda³, Lumir Krejci², Simon J. Boulton¹ - Show less +8 more•Institutions (5)

Francis Crick Institute¹, Masaryk University², Imperial College London³, Genentech⁴, University of Virginia⁵

16 Jul 2015-Cell (Elsevier)-Vol. 162, Iss: 2, pp 271-286

TL;DR: It is proposed that Rad51 paralogs stimulate HR by remodeling the Rad51 filament, priming it for strand exchange with the template duplex, demonstrating that remodeling is essential for RFS-1/RIP-1 function.

read less

About: This article is published in Cell.The article was published on 2015-07-16 and is currently open access. It has received 127 citations till now. The article focuses on the topics: RAD51 & Homologous recombination.

...read moreread less

Citations

PDF

Open Access

More filters

Journal Article•DOI•

Homologous recombination and the repair of DNA Double-Strand Breaks

[...]

William Douglass Wright, Shanaya Shital Shah, Wolf Dietrich Heyer¹•Institutions (1)

University of California, Davis¹

06 Jul 2018-Journal of Biological Chemistry

TL;DR: The DNA transactions and enzymatic activities required for this elegantly orchestrated process in the context of the repair of DNA double-strand breaks in somatic cells are discussed.

...read moreread less

406 citations

Cites background from "Rad51 Paralogs Remodel Pre-synaptic..."

...The functions of the Rad51 paralogs appear to be accomplished through their integration into the Rad51 filament (45, 46), although their arrangement of contacts and frequency within or capping filament segments is unknown....
[...]
...Rad51 paralog-dependent changes in nucleoprotein–ssDNA nuclease sensitivity suggest their interaction with Rad51 filaments leads to changes in its conformation (46)....
[...]

Journal Article•

Combined functional genomic maps of the C-elegans DNA damage response

[...]

Marc Vidal, Simon J. Boulton, Anton Gartner¹, Jérôme Reboul, Philippe Vaglio, Nicholas J. Dyson, David E. Hill - Show less +3 more•Institutions (1)

Max Planck Society¹

01 Dec 2002-Chemical Research in Toxicology

TL;DR: In this article, a strategy that combines protein-protein interaction mapping and large-scale phenotypic analysis in Caenorhabditis elegans was used to identify 12 worm DDR orthologs and 11 novel DDR genes.

...read moreread less

Abstract: Many human cancers originate from defects in the DNA damage response (DDR). Although much is known about this process, it is likely that additional DDR genes remain to be discovered. To identify such genes, we used a strategy that combines protein-protein interaction mapping and large-scale phenotypic analysis inCaenorhabditis elegans. Together, these approaches identified 12 worm DDR orthologs and 11 novel DDR genes. One of these is the putative ortholog of hBCL3, a gene frequently altered in chronic lymphocytic leukemia. Thus, the combination of functional genomic mapping approaches in model organisms may facilitate the identification and characterization of genes involved in cancer and, perhaps, other human diseases.

...read moreread less

264 citations

Journal Article•DOI•

Main steps in DNA double-strand break repair: an introduction to homologous recombination and related processes.

[...]

Lepakshi Ranjha¹, Sean M. Howard¹, Petr Cejka², Petr Cejka¹•Institutions (2)

University of Lugano¹, ETH Zurich²

11 Jan 2018-Chromosoma

TL;DR: In this paper, the main pathways of eukaryotic DNA double-strand break repair with the focus on homologous recombination and its various subpathways are reviewed.

...read moreread less

Abstract: DNA double-strand breaks arise accidentally upon exposure of DNA to radiation and chemicals or result from faulty DNA metabolic processes. DNA breaks can also be introduced in a programmed manner, such as during the maturation of the immune system, meiosis, or cancer chemo- or radiotherapy. Cells have developed a variety of repair pathways, which are fine-tuned to the specific needs of a cell. Accordingly, vegetative cells employ mechanisms that restore the integrity of broken DNA with the highest efficiency at the lowest cost of mutagenesis. In contrast, meiotic cells or developing lymphocytes exploit DNA breakage to generate diversity. Here, we review the main pathways of eukaryotic DNA double-strand break repair with the focus on homologous recombination and its various subpathways. We highlight the differences between homologous recombination and end-joining mechanisms including non-homologous end-joining and microhomology-mediated end-joining and offer insights into how these pathways are regulated. Finally, we introduce noncanonical functions of the recombination proteins, in particular during DNA replication stress.

...read moreread less

213 citations

Journal Article•DOI•

Replication Fork Reversal: Players and Guardians

[...]

Annabel Quinet¹, Delphine Lemaçon¹, Alessandro Vindigni¹•Institutions (1)

Saint Louis University¹

07 Dec 2017-Molecular Cell

TL;DR: Recent findings that uncover key molecular determinants for reversed fork formation are summarized and how the homologous recombination factors BRCA1, BRCa2, and RAD51 protect these structures from extended nucleolytic degradation is described.

...read moreread less

193 citations

Cites background from "Rad51 Paralogs Remodel Pre-synaptic..."

...…to determine whether alternative HR mediators—e.g., MMS22L-TONSL (Piwko et al., 2016), the RAD51 paralogs (RAD51B, RAD51C, RAD51D, XRCC2, and XRCC3) (Taylor et al., 2015), and RAD54 (Bugreev et al., 2011)—may assist RAD51 nucleofilament formation and replication fork reversal in the absence of…...
[...]
...Another important avenue of future investigation is to determine whether alternative HR mediators—e.g., MMS22L-TONSL (Piwko et al., 2016), the RAD51 paralogs (RAD51B, RAD51C, RAD51D, XRCC2, and XRCC3) (Taylor et al., 2015), and RAD54 (Bugreev et al., 2011)—may assist RAD51 nucleofilament formation and replication fork reversal in the absence of BRCA2....
[...]

Journal Article•

Main steps in DNA double-strand break repair

[...]

Lepakshi Ranjha¹, Sean M. Howard¹, Petr Cejka¹•Institutions (1)

University of Lugano¹

11 Jan 2018-Chromosoma

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.

...read moreread less

172 citations

Cites background from "Rad51 Paralogs Remodel Pre-synaptic..."

...…model system instead suggests that the RAD51 paralogs, represented by RFS-1 and RIP-1, function downstream of BRCA2, specifically in the stabilization of the RAD51 nucleoprotein filament and its remodeling into a species that is optimally capable to invade template dsDNA (Taylor et al. 2015, 2016)....
[...]

1
2
3
4
…
5
6
7
8
9
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26

Collapse

References

PDF

Open Access

More filters

Journal Article•DOI•

Identification of the breast cancer susceptibility gene BRCA2

[...]

Richard Wooster, Graham R. Bignell, Johnathan M. Lancaster¹, Sally Swift, Sheila Seal, Jonathon Mangion, N. Collins, Simon G. Gregory², Curtis Gumbs³, Gos Micklem² - Show less +6 more•Institutions (3)

National Institutes of Health¹, Wellcome Trust Sanger Institute², Duke University³

21 Dec 1995-Nature

TL;DR: The identification of a gene in which six different germline mutations in breast cancer families that are likely to be due to BRCA2 are detected, and results indicate that this is the BRC a2 gene.

...read moreread less

Abstract: IN Western Europe and the United States approximately 1 in 12 women develop breast cancer. A small proportion of breast cancer cases, in particular those arising at a young age, are attributable to a highly penetrant, autosomal dominant predisposition to the disease. The breast cancer susceptibility gene, BRCA2, was recently localized to chromosome 13q12-q13. Here we report the identification of a gene in which we have detected six different germline mutations in breast cancer families that are likely to be due to BRCA2. Each mutation causes serious disruption to the open reading frame of the transcriptional unit. The results indicate that this is the BRCA2 gene.

...read moreread less

3,333 citations

"Rad51 Paralogs Remodel Pre-synaptic..." refers background in this paper

...…are mutated in Fanconi anemia and breast and ovarian cancer (Howlett et al., 2002; Lancaster et al., 1996; Rahman et al., 2007; Reid et al., 2007; Wooster et al., 1995; Xia et al., 2007), biallelic germlinemutations in RAD51C cause a severe form of Fanconi anemia (Vaz et al., 2010), whereas…...
[...]

Journal Article•DOI•

Mechanism of eukaryotic homologous recombination.

[...]

Joseph San Filippo¹, Patrick Sung¹, Hannah L. Klein²•Institutions (2)

Yale University¹, New York University²

02 Jun 2008-Annual Review of Biochemistry

TL;DR: HR accessory factors that facilitate other stages of the Rad51- and Dmc1-catalyzed homologous DNA pairing and strand exchange reaction have also been identified.

...read moreread less

Abstract: Homologous recombination (HR) serves to eliminate deleterious lesions, such as double-stranded breaks and interstrand crosslinks, from chromosomes. HR is also critical for the preservation of repli- cation forks, for telomere maintenance, and chromosome segrega- tion in meiosis I. As such, HR is indispensable for the maintenance of genome integrity and the avoidance of cancers in humans. The HR reaction is mediated by a conserved class of enzymes termed recombinases. Two recombinases, Rad51 and Dmc1, catalyze the pairing and shuffling of homologous DNA sequences in eukaryotic cells via a filamentous intermediate on ssDNA called the presynaptic filament. The assembly of the presynaptic filament is a rate-limiting process that is enhanced by recombination mediators, such as the breast tumor suppressor BRCA2. HR accessory factors that facil- itate other stages of the Rad51- and Dmc1-catalyzed homologous DNA pairing and strand exchange reaction have also been identified. Recent progress on elucidating the mechanisms of action of Rad51 and Dmc1 and their cohorts of ancillary factors is reviewed here.

...read moreread less

1,542 citations

"Rad51 Paralogs Remodel Pre-synaptic..." refers background in this paper

...HR is regulated by mediator proteins, including BRCA2, Rad54, and the family of Rad51 paralogs (San Filippo et al., 2008), which appear to act as positive regulators at different steps of the HR reaction....
[...]
...Unloading of Rad51 from double-stranded DNA (dsDNA) permits the initiation of repair DNA synthesis and the resulting joint molecules are processed by various enzymes to complete the repair reaction (Chapman et al., 2012; San Filippo et al., 2008)....
[...]
...1DNA Damage Response Laboratory, Clare Hall Laboratory, The Francis Crick Institute, South Mimms EN6 3LD, UK 2Department of Biology, Masaryk University, 62500 Brno, Czech Republic 3International Clinical Research Center, St. Anne’s University Hospital in Brno, 62500 Brno, Czech Republic 4National Centre for Biomolecular Research, Masaryk University, 62500 Brno, Czech Republic 5Section of Virology, Single Molecule Imaging Group and MRC Clinical Sciences Centre, Department of Medicine, Imperial College London, London W12 0NN, UK 6UCSF-Mission Bay, Genentech Hall S574, San Francisco, CA 94158, USA 7Electron Microscopy Science Technology Platform, Lincoln’s Inn Fields Laboratory, The Francis Crick Institute, London WC2A 3LY, UK 8Department of Biochemistry and Molecular Genetics, University of Virginia School of Medicine, Charlottesville, VA 22908, USA *Correspondence: lkrejci@chemi.muni.cz (L.K.), simon.boulton@crick.ac.uk (S.J.B.) http://dx.doi.org/10.1016/j.cell.2015.06.015 This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/)....
[...]

Journal Article•DOI•

Playing the End Game: DNA Double-Strand Break Repair Pathway Choice

[...]

J. Ross Chapman¹, Martin R.G. Taylor¹, Simon J. Boulton¹•Institutions (1)

London Research Institute¹

24 Aug 2012-Molecular Cell

TL;DR: Recent insights are reviewed into the mechanisms that influence the choice between competing DSB repair pathways, how this is regulated during the cell cycle, and how imbalances in this equilibrium result in genome instability.

...read moreread less

1,427 citations

"Rad51 Paralogs Remodel Pre-synaptic..." refers background in this paper

...Unloading of Rad51 from double-stranded DNA (dsDNA) permits the initiation of repair DNA synthesis and the resulting joint molecules are processed by various enzymes to complete the repair reaction (Chapman et al., 2012; San Filippo et al., 2008)....
[...]

Journal Article•DOI•

XRCC3 promotes homology-directed repair of DNA damage in mammalian cells

[...]

Andrew J. Pierce¹, Roger D. Johnson², Larry H. Thompson³, Maria Jasin²•Institutions (3)

Memorial Sloan Kettering Cancer Center¹, Cornell University², Lawrence Livermore National Laboratory³

15 Oct 1999-Genes & Development

TL;DR: It is demonstrated here that error-free homology-directed repair of DNA double-strand breaks is decreased 25-fold in an XR CC3-deficient hamster cell line and can be restored to wild-type levels through XRCC3 expression.

...read moreread less

Abstract: Homology-directed repair of DNA damage has recently emerged as a major mechanism for the maintenance of genomic integrity in mammalian cells. The highly conserved strand transferase, Rad51, is expected to be critical for this process. XRCC3 possesses a limited sequence similarity to Rad51 and interacts with it. Using a novel fluorescence-based assay, we demonstrate here that error-free homology-directed repair of DNA double-strand breaks is decreased 25-fold in an XRCC3-deficient hamster cell line and can be restored to wild-type levels through XRCC3 expression. These results establish that XRCC3-mediated homologous recombination can reverse DNA damage that would otherwise be mutagenic or lethal.

...read moreread less

1,275 citations

"Rad51 Paralogs Remodel Pre-synaptic..." refers background in this paper

...…formation after DNA damage, suggestive of a major function at an early stage in the HR reaction (Chun et al., 2013; French et al., 2002; Gasior et al., 1998; Godthelp et al., 2002; Hays et al., 1995; Johnson et al., 1999; Pierce et al., 1999; Rattray and Symington, 1995; Takata et al., 2000, 2001)....
[...]

Journal Article•DOI•

Biallelic Inactivation of BRCA2 in Fanconi Anemia

[...]

Niall G. Howlett¹, Toshiyasu Taniguchi¹, Susan B. Olson², Barbara Cox², Quinten Waisfisz, Christine E. M. de Die-Smulders³, Nicole Persky¹, Markus Grompe², Hans Joenje, Gerard Pals, Hideyuki Ikeda⁴, Edward A. Fox¹, Alan D. D'Andrea¹ - Show less +9 more•Institutions (4)

Harvard University¹, Oregon Health & Science University², Maastricht University Medical Centre³, Sapporo Medical University⁴

26 Jul 2002-Science

TL;DR: It is shown that cell lines derived from FA-B and FA-D1 patients have biallelic mutations in BRCA2 and express truncated BRC a2 proteins, which may result in cancer risks similar to those observed in families withBRCA1 or BRCa2 mutations.

...read moreread less

Abstract: Fanconi anemia (FA) is a rare autosomal recessive cancer susceptibility disorder characterized by cellular hypersensitivity to mitomycin C (MMC). Six FA genes have been cloned, but the gene or genes corresponding to FA subtypes B and D1 remain unidentified. Here we show that cell lines derived from FA-B and FA-D1 patients have biallelic mutations in BRCA2 and express truncated BRCA2 proteins. Functional complementation of FA-D1 fibroblasts with wild-type BRCA2 complementary DNA restores MMC resistance. Our results link the six cloned FA genes with BRCA1 and BRCA2 in a common pathway. Germ-line mutation of genes in this pathway may result in cancer risks similar to those observed in families with BRCA1 or BRCA2 mutations.

...read moreread less

1,144 citations

"Rad51 Paralogs Remodel Pre-synaptic..." refers background in this paper

...Like BRCA2 and PALB2, which are mutated in Fanconi anemia and breast and ovarian cancer (Howlett et al., 2002; Lancaster et al., 1996; Rahman et al., 2007; Reid et al., 2007; Wooster et al., 1995; Xia et al., 2007), biallelic germlinemutations in RAD51C cause a severe form of Fanconi anemia (Vaz et…...
[...]