The meiosis-specific recombinase hDmc1 forms ring structures and interacts with hRad51

Masson, Jean‐Yves; Davies, Adelina A.; Hajibagheri, Nasser; Dyck, Eric Van; Benson, Fiona E.; Stasiak, Alicja Z.; Stasiak, Andrzej; West, Stephen C.

doi:10.1093/emboj/18.22.6552

Cited by 113 publications

(105 citation statements)

References 67 publications

(104 reference statements)

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“…The protein concentrations used in the experiments were 0 M (lanes 1, 5, 9, 13, 17, 21, 25, 29, and 33), 2 M (lanes 2, 6, 10, 14, 18, 22, 26, 30, and 34), 4 M (lanes 3, 7, 11, 15, 19, 23, 27, 31, and 35), and 8 M (lanes 4, 8, 12, 16, 20, 24, 28, 32, and 36). [6][7][8][10][11][12][14][15][16][18][19][20][22][23][24][26][27][28][30][31][32][34][35][36] (Ref. 36 and Fig.…”

Section: Tbpip/hop2 Enhances the Dmc1-mediated Homologous Pairingmentioning

confidence: 99%

Positive Role of the Mammalian TBPIP/HOP2 Protein in DMC1-mediated Homologous Pairing

Enomoto¹,

Kinebuchi²,

Sato

et al. 2004

Journal of Biological Chemistry

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In meiosis, homologous recombination preferentially occurs between homologous chromosomes rather than between sister chromatids, which is opposite to the bias of mitotic recombinational repair. The TBPIP/HOP2 protein is a factor that ensures the proper pairing of homologous chromosomes during meiosis. In the present study, we found that the purified mouse TBPIP/ HOP2 protein stimulated homologous pairing catalyzed by the meiotic DMC1 recombinase in vitro. In contrast, TBPIP/HOP2 did not stimulate homologous pairing by RAD51, which is another homologous pairing protein acting in both meiotic and mitotic recombination. The positive effect of TBPIP/HOP2 in the DMC1-mediated homologous pairing was only observed when TBPIP/ HOP2 first binds to double-stranded DNA, not to singlestranded DNA, before the initiation of the homologous pairing reaction. Deletion analyses revealed that the C-terminal basic region of TBPIP/HOP2 is required for efficient DNA binding and is also essential for its homologous pairing stimulation activity. Therefore, these results suggest that TBPIP/HOP2 directly binds to DNA and functions as an activator for DMC1 during the homologous pairing step in meiosis.During meiosis, two successive rounds of nuclear division, meiosis I and meiosis II, are promoted with a single round of DNA replication. As a result, diploid cells produce haploid gametes in eukaryotes. In the cell division at meiosis I, homologous chromosomes are aligned, and a high level of recombination occurs between homologous chromosomes but not between sister chromatids. This preferential recombination between homologous chromosomes, called homologous recombination, ensures their correct segregation at meiosis I through the formation of chiasmata, which physically connect homologous chromosomes.Homologous recombination is initiated by double strand break (DSB) 1 formation by SPO11 at the initiation sites for recombination (1-3). Then a single-stranded DNA (ssDNA) tail derived from a DSB site invades the homologous doublestranded DNA (dsDNA) to form a heteroduplex. This strand invasion step, called homologous pairing, is the key step in homologous recombination. In Escherichia coli, the RecA protein catalyzes the homologous pairing step (4, 5). Two eukaryotic homologues of RecA, the RAD51 and DMC1 proteins, which are conserved from yeast to human, have been identified (6 -9) and have been shown to catalyze homologous pairing in vitro (10 -15). The RAD51 gene is expressed in both mitotic and meiotic cells, but the DMC1 gene functions only in meiotic cells. Disruption of the Rad51 gene results in early embryonic lethality in mice (16,17). In chicken DT40 cells, the RAD51 gene disruption causes the accumulation of spontaneous chromosomal breaks and significantly reduces the recombination frequency between sister chromatids (18,19). In contrast, disruption of the Dmc1 gene does not cause lethality in mice, but the dmc1 knock-out mice are sterile with an arrest of gametogenesis in the first meiotic prophase (20,21). Therefore, DMC1 is a me...

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Section: Tbpip/hop2 Enhances the Dmc1-mediated Homologous Pairingmentioning

confidence: 99%

Positive Role of the Mammalian TBPIP/HOP2 Protein in DMC1-mediated Homologous Pairing

Enomoto¹,

Kinebuchi²,

Sato

et al. 2004

Journal of Biological Chemistry

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“…Dmc1 was also proposed to be a structural and functional relative of RecA based on mutant and sequence analysis (Bishop et al 1992;Story et al 1993). Biochemical demonstration of recombinase activity for Rad51 and Dmc1 supports the idea that each protein promotes strand exchange by a mechanism related to that of RecA (Sung 1994;Baumann et al 1996;Li et al 1997;Masson et al 1999;Hong et al 2001). Although similar in several respects, electron microscopy (EM) analysis showed that Dmc1 and Rad51 differ in that Dmc1 has a strong tendency to form tori and can bind DNA in the toroid form Passy et al 1999;Kinebuchi et al 2004).…”

mentioning

confidence: 92%

Red-Hed regulation: recombinase Rad51, though capable of playing the leading role, may be relegated to supporting Dmc1 in budding yeast meiosis: Figure 1.

Sheridan

Bishop²

2006

Genes Dev.

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DNA strand exchange is the central process of homologous recombination. In budding yeast, this reaction is catalyzed by the recombinases Rad51 and Dmc1. Rad51 is responsible for recombinational repair of DNA damage during mitosis and is also important during meiotic recombination. Dmc1 is only expressed during meiosis and is required for meiotic recombination. The discovery that these two different recombinases are needed for normal levels of meiotic recombination in budding yeast raised the question of how the functions of these proteins relate to one another. The paper by Tsubouchi and Roeder (2006) in this issue of Genes & Development represents important progress toward what is apparently a rather complex answer. Tsubouchi and Roeder (2006) report discovery of a novel meiosis-specific protein, Hed1, which appears to inhibit Rad51 when Dmc1 is absent. The authors show mutation of the HED1 gene allows cells to bypass the meiotic arrest caused by a dmc1 mutation and resolve meiosis-specific double-strand breaks (DSBs) using Rad51. A hed1 mutation can also suppress the defects caused by mutation of HOP2, which codes for a Dmc1 accessory factor. Two-hybrid experiments show that Hed1 and Rad51 can interact directly and immuno-staining shows that subnuclear foci formed by Hed1 and Rad51 colocalize. Together these results imply that Hed1's influence on Rad51 activity is direct. Furthermore, expression of Hed1 in mitotic cells provided evidence that Hed1 expression can be sufficient to inhibit Rad51-dependent repair of mitotic DNA damage.A reasonable interpretation of these results is that the meiotic recombination machinery of budding yeast is regulated such that Dmc1 carries out most strand exchange. Tsubouchi and Roeder's (2006) results also add to evidence indicating that Rad51 is capable of replacing Dmc1's function under certain circumstances. Here, we place these new findings in the context of previous observations and present a model to explain how Rad51 and Dmc1 may cooperate to promote interhomolog recombination in budding yeast, while at the same time accounting for the observed functional redundancy. We further speculate as to how the functional relationship of Rad51 and Dmc1 may have evolved.The notion that Rad51 activity is blocked during meiosis is not new. Previous work showed that Dmc1-independent recombination is inhibited by proteins associated with axial elements (Schwacha and Kleckner 1997;Xu et al. 1997;Bishop et al. 1999;Niu et al. 2005) proteinaceous structures that organize pairs of sister chromatids into two parallel sets of loops by binding at their base. The assembly of the synaptonemal complex brings an axial element with its pair of sisters into close parallel alignment with another axial element holding the homologous sister pair. Three interacting axis-associated proteins-Red1, Hop1, and Mek1-regulate recombination by suppressing Dmc1-independent recombination and, in the case of Red1 and Hop1, by enhancing the efficiency of DSB formation in a locus-specific manner (Rockmill and Roeder...

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“…The molecular activities of RAD51 and DMC1 proteins have been studied in depth in vitro. Both proteins form helical structures on ssDNA and mediate the invasion of those so-called presynaptic filaments into homologous duplex DNA to form displacement loops (Shinohara et al, 1992;Ogawa et al, 1993;Benson et al, 1994;Sung, 1994;Baumann et al, 1996;Li et al, 1997;Masson et al, 1999;Hong et al, 2001;Sehorn et al, 2004;Yu and Egelman, 2010). Although similar in structure, some differences between the two recombinases may exist.…”

Section: Introductionmentioning

confidence: 99%

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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The meiosis-specific recombinase hDmc1 forms ring structures and interacts with hRad51

Cited by 113 publications

References 67 publications

Positive Role of the Mammalian TBPIP/HOP2 Protein in DMC1-mediated Homologous Pairing

Positive Role of the Mammalian TBPIP/HOP2 Protein in DMC1-mediated Homologous Pairing

Red-Hed regulation: recombinase Rad51, though capable of playing the leading role, may be relegated to supporting Dmc1 in budding yeast meiosis: Figure 1.

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

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