Saccharomyces cerevisiae recA homologues RAD51 and DMC1 have both distinct and overlapping roles in meiotic recombination

Shinohara, Atsushi; Gasior, Stephen L.; Ogawa, Tomoko; Kleckner, Nancy; Bishop, Douglas K.

doi:10.1046/j.1365-2443.1997.1480347.x

Cited by 188 publications

(183 citation statements)

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“…Finally, in vivo experiments suggest another accessory protein, Hop2-Mnd1, stimulates Dmc1-dependent and not Rad51-dependent recombination in vivo (Tsubouchi and Roeder 2003;Chen et al 2004;Henry et al 2006). Although these accessory factor differences may allow for distinct regulation of the two recombinases, we reiterate that the ability of each of the recombinases to promote substantial strand invasion in the absence of the other indicates a significant degree of functional redundancy in vivo (Schwacha and Kleckner 1997;Shinohara et al 1997;Zenvirth et al 1997;Bishop et al 1999;Tsubouchi and Roeder 2003).…”

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confidence: 70%

“…Assembly of Rad51 at DSB sites is promoted by both Rad52 and Rad55-Rad57 (Gasior et al 2001), while assembly of Dmc1 is partially dependent on Rad51 (Bishop 1994;Shinohara et al 1997) and its activity also depends on the Sae3-Mei5 protein (Hayase et al 2004;Tsubouchi and Roeder 2004). Two additional factors, Rad54 and Tid1/ Rdh54, are capable of stimulating the activity of both recombinases (Tan et al 2003;E.…”

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confidence: 99%

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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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confidence: 99%

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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“…In lily, however, although these two proteins colocalize on or adjacent to chromosomes from leptotene on to zygotene, the DMC1 foci disappear but the RAD51 foci retain at pachytene, indicating that RAD51 might have a late function after crossover formation [95]. Furthermore, in the budding yeast, normal loading of DMC1 onto chromosomes seems to be dependent on the presence of RAD51, as DMC1 foci are detectable but reduced in rad51 mutants, but RAD51 foci are normal in dmc1 mutants [77,78].…”

Section: Dsb Processing and Function Of Reca Proteinsmentioning

confidence: 99%

“…The yeast RAD51 interacts directly with RAD54, a member of SWI2/MOT1 family [76]. Detailed analysis of the dmc1 and rad51 mutants suggests that these two genes perform both overlapping and distinct functions in meiotic recombination [77]. Interestingly, these two proteins may share the same or similar recombination functions, because they can substitute each other under certain circumstances.…”

Section: Dsb Processing and Function Of Reca Proteinsmentioning

confidence: 99%

“…However, double mutant studies of red1 with dmc1 and rad51 provide evidences supporting the conclusion that the functions of these two proteins are not identical [77]. RED1 is a phosphoprotein that serves as a structural component of axial element, and is important for synapsis and the establishment of an interhomolog-specific recombination pathway by promoting DSB formation [99][100][101].…”

Section: Dsb Processing and Function Of Reca Proteinsmentioning

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Double-stranded DNA breaks and gene functions in recombination and meiosis

Mā

2006

Cell Res

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Gene functions in recombination and meiosis 402 npg REVIEW Meiotic prophase I is a long and complex phase. Homologous recombination is an important process that occurs between homologous chromosomes during meiotic prophase I. Formation of chiasmata, which hold homologous chromosomes together until the metaphase I to anaphase I transition, is critical for proper chromosome segregation. Recent studies have suggested that the SPO11 proteins have conserved functions in a number of organisms in generating sites of double-stranded DNA breaks (DSBs) that are thought to be the starting points of homologous recombination. Processing of these sites of DSBs requires the function of RecA homologs, such as RAD51, DMC1, and others, as suggested by mutant studies; thus the failure to repair these meiotic DSBs results in abnormal chromosomal alternations, leading to disrupted meiosis. Recent discoveries on the functions of these RecA homologs have improved the understanding of the mechanisms underlying meiotic homologous recombination.Cell Research (2006) Meiosis is a highly coordinated cell division, which generates four haploid reproductive cells required for sexual reproduction. Meiosis involves one round of DNA replication and two nuclear divisions, meiosis I and meiosis II. The first nuclear division leads to the segregation of homologous chromosomes (homologs), and is unique to meiosis. During the second division, sister chromatids are separated, resulting in the formation of four haploid nuclei and followed by the meiotic cytokinesis that forms four haploid cells. Similar to mitosis, both meiosis I and meiosis II can be divided into four stages: prophase, metaphase, anaphase, and telophase.However, meiosis I differs from meiosis II as meiosis I involves homology search, pairing, interhomolog recombination, and synapsis of homologs, processes that are required for correct association and segregation of homologs. The prophase stage of meiosis I, or prophase I, has been the target of interest because of the occurrence of these major processes of chromosome interactions. During early prophase I, arms of sister chromosomes are closely associated by protein complexes called cohesins, which are removed during the metaphase I/anaphase I transition. However, the centromere regions remained associated until the segregation of sister chromatids during meiosis II. Homologous pairing is the result of interaction between homologous chromosomes relying on the homology of DNA sequences [1,2], and is considered to be a transient and non-stable association between homologous chromosomes. Pairing between homologous chromosomes facilitates the process of recombination. The recombination process confers the interexchange of genetic information between non-sister chromatids, and generates chiasmata, which ensure proper association between homologous chromosomes prior to chromosome segregation at anaphase I. Synapsis, however, is a stable association by forming synaptonemal complexes between chromosomes. Synaptonemal complexes are threeparti...

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Meiotic Recombination in Mammals

Santucci‐Darmanin

Baudat

2010

Oogenesis

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Saccharomyces cerevisiae recA homologues RAD51 and DMC1 have both distinct and overlapping roles in meiotic recombination

Cited by 188 publications

References 39 publications

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

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

Double-stranded DNA breaks and gene functions in recombination and meiosis

Meiotic Recombination in Mammals

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