Tid1/Rdh54 promotes colocalization of Rad51 and Dmc1 during meiotic recombination

Shinohara, Miki; Gasior, Stephen L.; Bishop, Douglas K.; Shinohara, Atsushi

doi:10.1073/pnas.97.20.10814

Cited by 197 publications

(249 citation statements)

References 45 publications

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“…It was previously suggested that Rad51 might load on one end formed by a DSB while Dmc1 loads on the other (Shinohara et al 2000). This hypothetical configuration works well with the present proposal, although other configurations allowing for support of Dmc1 by Rad51 can be imagined as well.…”

Section: A Model For the Contribution Of Dmc1 And Rad51 To Interhomolsupporting

confidence: 73%

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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Section: A Model For the Contribution Of Dmc1 And Rad51 To Interhomolsupporting

confidence: 73%

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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“…Consistent with this are immunological observations that reveal a side-by-side distribution of the two recombinases (Tarsounas et al 1999;Shinohara et al 2000). In addition, biochemical studies indicate that the two ends of the resected DSB behave differently, with one, proposed to be Dmc1-coated, responsible for the initial strand invasion of the homolog, while the second is captured at a later stage in the recombination pathway (Hunter and Kleckner 2001).…”

Section: Chromatin Loading Of Atdmc1 and Atrad51 Is Asynchronoussupporting

confidence: 72%

“…Studies in budding yeast have led to the proposal that there may be inherent asymmetry in the way that Dmc1 and Rad51 interact with the two ends of the meiotic DSBs (Shinohara et al 2000;Hunter and Kleckner 2001). Consistent with this are immunological observations that reveal a side-by-side distribution of the two recombinases (Tarsounas et al 1999;Shinohara et al 2000).…”

Section: Chromatin Loading Of Atdmc1 and Atrad51 Is Asynchronousmentioning

confidence: 99%

ASY1 mediates AtDMC1-dependent interhomolog recombination during meiosis in Arabidopsis

Sanchez‐Moran¹,

Santos²,

Jones³

et al. 2007

Genes Dev.

250

326

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ASY1 is an Arabidopsis protein required for synapsis and crossover formation during meiosis. The chronology of meiotic recombination has been investigated in wild type and an asy1 mutant. We observe a delay between the appearance of chromatin-associated AtSPO11-1 foci and DNA double-strand break (DSB) formation, which occurs contemporaneously with chromosome axis formation and transition of ASY1 from chromatin-associated foci to a linear axis-associated signal. DSBs are formed independently of ASY1 in an AtSPO11-1-dependent manner. They are partially restored in Atspo11-1-3 using cisplatin, but their control appears abnormal. Axis morphogenesis is independent of ASY1, but axis structure may be compromised in asy1. Localization of the strand exchange proteins AtRAD51 and AtDMC1 to the chromatin occurs asynchronously shortly after DSB formation, with AtDMC1 localizing in advance of AtRAD51. In wild-type nuclei, both recombinases form numerous foci that persist for ∼12 h before gradually decreasing in number. In asy1, initial localization of AtDMC1 is normal, but declines abruptly such that interhomolog recombination is severely compromised. Limited ASY1-independent, DMC1-dependent interhomolog recombination remains, but appears restricted to subtelomeric sequences where the homologs are fortuitously in proximity. Thus, ASY1 plays a key role in coordinating the activity of the RecA homologs to create a bias in favor of interhomolog recombination.

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“…Much of our current understanding of the mechanism of meiotic recombination comes from studies carried out in yeast, partly because rad51 mutants are viable in this organism. In S. cerevisiae, the appearance of Dmc1/Rad51 foci coincides with the formation of Spo11-induced DSBs, and the foci tend to disappear as the chromosomes synapse (Shinohara et al, 2000).…”

Section: Predominant In G1mentioning

confidence: 99%

BRCA2: a universal recombinase regulator

2007

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Homologous recombination has a dual role in eukaryotic organisms. Firstly, it is responsible for the creation of genetic variability during meiosis by directing the formation of reciprocal crossovers that result in random combinations of alleles and traits. Secondly, in mitotic cells, it maintains the integrity of the genome by promoting the faithful repair of DNA double-strand breaks (DSBs). In vertebrates, it therefore plays a key role in tumour avoidance. Mutations in the tumour suppressor protein BRCA2 are associated with predisposition to breast and ovarian cancers, and loss of BRCA2 function leads to genetic instability. BRCA2 protein interacts directly with the RAD51 recombinase and regulates recombinationmediated DSB repair, accounting for the high levels of spontaneous chromosomal aberrations seen in BRCA2-defective cells. Recent observations indicate that BRCA2 also plays a critical role in meiotic recombination, this time through direct interactions with the meiosis-specific recombinase DMC1. The interactions of BRCA2 with RAD51 and DMC1 lead us to suggest that the BRCA2 tumour suppressor is a universal regulator of recombinase actions.

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Tid1/Rdh54 promotes colocalization of Rad51 and Dmc1 during meiotic recombination

Cited by 197 publications

References 45 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.

ASY1 mediates AtDMC1-dependent interhomolog recombination during meiosis in Arabidopsis

BRCA2: a universal recombinase regulator

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