A comparative analysis of Dmc1 and Rad51 nucleoprotein filaments

Sheridan, Sean D.; Xiong, Yong; Roth, Robyn; Heuser, John E.; Sehorn, Michael G.; Sung, Patrick; Bishop, Douglas K.

doi:10.1093/nar/gkn352

Cited by 98 publications

(108 citation statements)

References 58 publications

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“…The results furthermore demonstrate that Arabidopsis DMC1 can act independently of RAD51 as a bona fide recombinase in vivo, because it promotes DNA repair, chromosome pairing (inferred from observed pachytene stages) ( Figure 1A), and synapsis (see Supplemental Figure 3 online) in atr rad51 double mutants. Our observations are consistent with the findings of in vitro recombinase activity of heterologously expressed and purified DMC1 proteins from various organisms and with Dmc1-mediated strand exchange activities observed in yeast rad51 mutants (Schwacha and Kleckner, 1997;Shinohara et al, 1997;Hong et al, 2001;Sheridan et al, 2008;Bugreev et al, 2010).…”

Section: A Mutation In Atr Suppresses the Severe Meiotic Defects Of Rsupporting

confidence: 92%

“…Our observations are in accordance with previous findings (reviewed in Kagawa and Kurumizaka, 2010) establishing that the ability to repair meiotic DSBs using homologous chromosomes as repair templates is predominantly associated with the DMC1 recombinase. To test whether this competence is an intrinsic property of the DMC1 protein itself or determined by accessory factors, as suggested earlier (Schwacha and Kleckner, 1997;Sheridan et al, 2008), we generated the atr rad51 asy1 triple mutant. The HORMA-domain protein ASY1 is part of the meiosis-specific chromosome axes and displays highest similarity to the yeast Hop1 protein (Sanchez-Moran et al, 2008).…”

Section: Asy1 Inhibits Dmc1-mediated Intersister Dna Repairmentioning

confidence: 99%

“…Recently, it has been shown that DMC1-mediated displacement loop structures are more resistant to helicase-mediated dissociation in vitro . Importantly, the activities of both proteins are modulated by a range of accessory proteins, accounting for the differences between RAD51 and DMC1 function in vivo (Sheridan and Bishop, 2006;Sheridan et al, 2008;Kagawa and Kurumizaka, 2010;Okorokov et al, 2010;Dray et al, 2011).…”

Section: Introductionmentioning

confidence: 99%

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The Recombinases DMC1 and RAD51 Are Functionally and Spatially Separated during Meiosis in Arabidopsis

et al. 2012

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Meiosis ensures the reduction of the genome before the formation of generative cells and promotes the exchange of genetic information between homologous chromosomes by recombination. Essential for these events are programmed DNA double strand breaks (DSBs) providing single-stranded DNA overhangs after their processing. These overhangs, together with the RADiation sensitive51 (RAD51) and DMC1 Disrupted Meiotic cDNA1 (DMC1) recombinases, mediate the search for homologous sequences. Current models propose that the two ends flanking a meiotic DSB have different fates during DNA repair, but the molecular details remained elusive. Here we present evidence, obtained in the model plant Arabidopsis thaliana, that the two recombinases, RAD51 and DMC1, localize to opposite sides of a meiotic DSB. We further demonstrate that the ATR kinase is involved in regulating DMC1 deposition at meiotic DSB sites, and that its elimination allows DMC1-mediated meiotic DSB repair even in the absence of RAD51. DMC1's ability to promote interhomolog DSB repair is not a property of the protein itself but the consequence of an ASYNAPTIC1 (Hop1)-mediated impediment for intersister repair. Taken together, these results demonstrate that DMC1 functions independently and spatially separated from RAD51 during meiosis and that ATR is an integral part of the regular meiotic program.

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Section: A Mutation In Atr Suppresses the Severe Meiotic Defects Of Rsupporting

confidence: 92%

Section: Asy1 Inhibits Dmc1-mediated Intersister Dna Repairmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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The Recombinases DMC1 and RAD51 Are Functionally and Spatially Separated during Meiosis in Arabidopsis

et al. 2012

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“…3B), which is comparable with the pitch obtained from AFM. Overall, the pitch values calculated using either method are equivalent to the numbers reported previously (41). AFM images also showed that, in contrast to filaments formed in Ca 2ϩ , Dmc1-dsDNA filaments formed in the presence of Mg 2ϩ appeared unstable and incomplete (supplemental Fig.…”

Section: Purified Recombinant Dmc1 and Tid1 Proteins Are Activesupporting

confidence: 83%

Saccharomyces cerevisiae Dmc1 and Rad51 Proteins Preferentially Function with Tid1 and Rad54 Proteins, Respectively, to Promote DNA Strand Invasion during Genetic Recombination

Nimonkar

Dombrowski

Siino

et al. 2012

Journal of Biological Chemistry

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Background: DNA strand exchange proteins Dmc1 and Rad51 and translocases Tid1 and Rad54 function in DNA break repair during meiosis.Results: We biochemically demonstrate that Dmc1 and Rad51 are specifically stimulated by Tid1 and Rad54, respectively. Conclusion: Dmc1-Tid1 and Rad51-Rad54 represent functional pairs for DNA pairing and joint molecule formation. Significance: The separate and independent functioning of these proteins offers insight into DNA pairing in meiosis.

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“…Discussion RAD51 and DMC1 share similar structure (Fig. 1A) and biochemical function (4,18). Because BRCA2 has been implicated in meiosis in multiple organisms through direct protein-protein interaction (5, 7-9), we set out to investigate the functional relevance of BRCA2-DMC1 binding and whether or not the BRC repeats, interaction sites for RAD51, bind DMC1.…”

Section: Brca2 Stimulates the Dna Strand Exchange By Dmc1 Overcomingmentioning

confidence: 99%

BRCA2 regulates DMC1-mediated recombination through the BRC repeats

Martinez

Nicolai

Kim

et al. 2016

Proc. Natl. Acad. Sci. U.S.A.

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In somatic cells, BRCA2 is needed for RAD51-mediated homologous recombination. The meiosis-specific DNA strand exchange protein, DMC1, promotes the formation of DNA strand invasion products (joint molecules) between homologous molecules in a fashion similar to RAD51. BRCA2 interacts directly with both human RAD51 and DMC1; in the case of RAD51, this interaction results in stimulation of RAD51-promoted DNA strand exchange. However, for DMC1, little is known regarding the basis and functional consequences of its interaction with BRCA2. Here we report that human DMC1 interacts directly with each of the BRC repeats of BRCA2, albeit most tightly with repeats 1-3 and 6-8. However, BRC1-3 bind with higher affinity to RAD51 than to DMC1, whereas BRC6-8 bind with higher affinity to DMC1, providing potential spatial organization to nascent filament formation. With the exception of BRC4, each BRC repeat stimulates joint molecule formation by DMC1. The basis for this stimulation is an enhancement of DMC1-ssDNA complex formation by the stimulatory BRC repeats. Lastly, we demonstrate that full-length BRCA2 protein stimulates DMC1-mediated DNA strand exchange between RPAssDNA complexes and duplex DNA, thus identifying BRCA2 as a mediator of DMC1 recombination function. Collectively, our results suggest unique and specialized functions for the BRC motifs of BRCA2 in promoting homologous recombination in meiotic and mitotic cells.T he breast cancer susceptibility protein 2, BRCA2, regulates RAD51-mediated homologous recombination (HR) (1-3). Both RAD51, a DNA strand exchange protein, and its meiotic counterpart, DMC1 (disrupted meiotic cDNA 1 or DNA meiotic recombinase 1), promote HR through the formation of a nucleoprotein filament on ssDNA (4). This filament finds and invades a homologous template, resulting in a DNA strand invasion product called a joint molecule or a displacement-loop (D-loop). The joint molecule provides a primer template for the new DNA synthesis required to repair the DNA double strand break (DSB).The first evidence implicating BRCA2 in meiosis came from studies in Ustilago maydis, where strains lacking the BRCA2 ortholog, Brh2, resulted in absence of meiotic products (5). Shortly thereafter, mouse BRCA2 was inferred to coordinate the activities of RAD51 and DMC1 (6). The first direct interaction between BRCA2 and DMC1 was observed in plants (7) and later in humans (8). In the plant, Arabidopsis thaliana, the interaction between Brca2 and Dmc1 was mapped to the BRC repeats (9), a highly conserved motif comprising a sequence of ∼35 amino acids that is present at least once in all BRCA2-like proteins (10). In humans, BRCA2 contains eight BRC repeats that bind with different affinities to RAD51, and they segregate into two functional classes (11). Within a BRC repeat, two motifs that bind RAD51 have been identified: one comprising the consensus sequence FxxA that mimics the oligomerization interface (12) and contacts the catalytic domain of RAD51; the other binding module comprises the alpha-helical region o...

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A comparative analysis of Dmc1 and Rad51 nucleoprotein filaments

Cited by 98 publications

References 58 publications

The Recombinases DMC1 and RAD51 Are Functionally and Spatially Separated during Meiosis in Arabidopsis

The Recombinases DMC1 and RAD51 Are Functionally and Spatially Separated during Meiosis in Arabidopsis

Saccharomyces cerevisiae Dmc1 and Rad51 Proteins Preferentially Function with Tid1 and Rad54 Proteins, Respectively, to Promote DNA Strand Invasion during Genetic Recombination

BRCA2 regulates DMC1-mediated recombination through the BRC repeats

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