Fission yeast Swi5/Sfr1 and Rhp55/Rhp57 differentially regulate Rhp51-dependent recombination outcomes

Akamatsu, Yufuko; Tsutsui, Yasuhiro; Morishita, Takashi; Siddique, S. P.; Kurokawa, Yumiko; Ikeguchi, Mitsunori; Yamao, Fumiaki; Arcangioli, Benoı̂t; Iwasaki, Hiroshi

doi:10.1038/sj.emboj.7601582

Cited by 81 publications

(105 citation statements)

References 40 publications

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“…The Rhp51 mediators Swi5/Sfr1 and Rhp55/57 are not exclusively redundant and may process DSBs differently (Akamatsu et al 2007). Mus81-Eme1 has been suggested to function in the Swi5-dependent pathway of HR repair, and depending on the DNA substrate, Swi5 can generate either Mus81-dependent crossovers or Mus81-independent noncrossovers (Hope et al 2007).…”

Section: Discussionmentioning

confidence: 99%

Mms22 Preserves Genomic Integrity During DNA Replication in Schizosaccharomyces pombe

Dovey

Russell

2007

Genetics

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The faithful replication of the genome, coupled with the accurate repair of DNA damage, is essential for the maintenance of chromosomal integrity. The MMS22 gene of Saccharomyces cerevisiae plays an important but poorly understood role in preservation of genome integrity. Here we describe a novel gene in Schizosaccharomyces pombe that we propose is a highly diverged ortholog of MMS22. Fission yeast Mms22 functions in the recovery from replication-associated DNA damage. Loss of Mms22 results in the accumulation of spontaneous DNA damage in the S-and G 2 -phases of the cell cycle and elevated genomic instability. There are severe synthetic interactions involving mms22 and most of the homologous recombination proteins but not the structure-specific endonuclease Mus81-Eme1, which is required for survival of broken replication forks. Mms22 forms spontaneous nuclear foci and colocalizes with Rad22 in cells treated with camptothecin, suggesting that it has a direct role in repair of broken replication forks. Moreover, genetic interactions with components of the DNA replication fork suggest that Mms2 functions in the coordination of DNA synthesis following damage. We propose that Mms22 functions directly at the replication fork to maintain genomic integrity in a pathway involving Mus81-Eme1.

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Section: Discussionmentioning

confidence: 99%

Mms22 Preserves Genomic Integrity During DNA Replication in Schizosaccharomyces pombe

Dovey

Russell

2007

Genetics

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“…The Swi5/Sfr1 recombination mediator appears to be particularly important for interhomolog exchanges in regions of DSB hotspots, while Rad22/Rti1 are proposed to function at intersister exchanges (Akamatsu et al 2007;Hyppa and Smith 2010). The Rad55/Rad57 mediator, which is distinct from Swi5/Sfr1, may be more important for exchanges in cold regions, affecting both interhomolog and intersister events (Khasanov et al 1999(Khasanov et al , 2008Akamatsu et al 2003;Hyppa and Smith 2010).…”

Section: S Pombe Rad16 Xpf Is Required For Normal Meiosismentioning

confidence: 99%

Increased Meiotic Crossovers and Reduced Genome Stability in Absence of Schizosaccharomyces pombe Rad16 (XPF)

Mastro¹,

Forsburg

2014

Genetics

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Schizosaccharomyces pombe Rad16 is the ortholog of the XPF structure-specific endonuclease, which is required for nucleotide excision repair and implicated in the single strand annealing mechanism of recombination. We show that Rad16 is important for proper completion of meiosis. In its absence, cells suffer reduced spore viability and abnormal chromosome segregation with evidence for fragmentation. Recombination between homologous chromosomes is increased, while recombination within sister chromatids is reduced, suggesting that Rad16 is not required for typical homolog crossovers but influences the balance of recombination between the homolog and the sister. In vegetative cells, rad16 mutants show evidence for genome instability. Similar phenotypes are associated with mutants affecting Rhp14 XPA but are independent of other nucleotide excision repair proteins such as Rad13 XPG . Thus, the XPF/XPA module of the nucleotide excision repair pathway is incorporated into multiple aspects of genome maintenance even in the absence of external DNA damage.T HE XPF/ERCC1 protein complex is one of several structurespecific endonucleases that function broadly as resolvases in the repair of damaged DNA (Schwartz and Heyer 2011). Rad16/Swi9 is the fission yeast ortholog of endonuclease XPF, which forms a complex with Swi10/Rad23 (ERCC1) (Carr et al. 1994). XPF has a conserved role in nucleotide excision repair (NER) to remove UV-induced lesions in the DNA (Camenisch et al. 2006;Gregg et al. 2011). In humans, mutation of XPF is associated with xeroderma pigmentosum (XP), which causes sun sensitivity and high rates of skin cancer, as well as premature aging and neurological disorders (Camenisch et al. 2006;Gregg et al. 2011). Recent studies suggest XPF mutations are also associated with Fanconi anemia (FA), which requires repair of interstrand crosslinks (ICLs) (Bogliolo et al. 2013;Kashiyama et al. 2013). The canonical model for NER suggests that upon recognition of helix-distorting lesions, the DNA is unwound to form a bubble around the damage. XPA (SpRhp14) loads XPF (SpRad16) and ERCC1 (SpSwi10); XPF cleaves at the 59 end of the bubble while XPG (SpRad13), another endonuclease, cleaves at the 39 end to remove the offending segment (Fagbemi et al. 2011;Schwartz and Heyer 2011). Thus, Schizosaccharomyces pombe rad16 mutants show a decrease in (6-4) photoproduct excision (McCready et al. 1993;Carr et al. 1994).Consistent with these clinical effects, XPF is implicated in multiple mechanisms of genome maintenance (Paques and Haber 1997;Gregg et al. 2011;Schwartz and Heyer 2011). XPF is required for single strand annealing (SSA), a form of double strand break (DSB) repair distinct from typical homologous recombination (HR) (Ma et al. 2003;Kass and Jasin 2010). This occurs when short regions of homology exposed by resection are able to pair, leaving nonhomologous 39 overhangs as substrates for XPF cleavage. In budding yeast, recruitment of ScRad1 XPF and ScRad10 ERCC1 in this pathway depends on interactions with other pro...

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“…Mammalian XRCC3 À / À or RAD51C À / À cell lines, and Schizosaccharomyces pombe rad57 mutants, which show reduced frequencies of DSB-induced recombination, also show alterations in the products recovered with an increase in long-tract gene conversion events (Brenneman et al 2002;Nagaraju et al 2006;Akamatsu et al 2007;Hope et al 2007). The long-tract events could be due to altered processing of recombination intermediates, perhaps in displacement of the invading strand.…”

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confidence: 99%

Role of the Saccharomyces cerevisiae Rad51 Paralogs in Sister Chromatid Recombination

2008

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Rad51 requires a number of other proteins, including the Rad51 paralogs, for efficient recombination in vivo. Current evidence suggests that the yeast Rad51 paralogs, Rad55 and Rad57, are important in formation or stabilization of the Rad51 nucleoprotein filament. To gain further insights into the function of the Rad51 paralogs, reporters were designed to measure spontaneous or double-strand break (DSB)-induced sister or nonsister recombination. Spontaneous sister chromatid recombination (SCR) was reduced 6000-fold in the rad57 mutant, significantly more than in the rad51 mutant. Although the DSBinduced recombination defect of rad57 was suppressed by overexpression of Rad51, elevated temperature, or expression of both mating-type alleles, the rad57 defect in spontaneous SCR was not strongly suppressed by these same factors. In addition, the UV sensitivity of the rad57 mutant was not strongly suppressed by MAT heterozygosity, even though Rad51 foci were restored under these conditions. This lack of suppression suggests that Rad55 and Rad57 have different roles in the recombinational repair of stalled replication forks compared with DSB repair. Furthermore, these data suggest that most spontaneous SCR initiates from single-stranded gaps formed at stalled replication forks rather than DSBs.

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Fission yeast Swi5/Sfr1 and Rhp55/Rhp57 differentially regulate Rhp51-dependent recombination outcomes

Cited by 81 publications

References 40 publications

Mms22 Preserves Genomic Integrity During DNA Replication in Schizosaccharomyces pombe

Mms22 Preserves Genomic Integrity During DNA Replication in Schizosaccharomyces pombe

Increased Meiotic Crossovers and Reduced Genome Stability in Absence of Schizosaccharomyces pombe Rad16 (XPF)

Role of the Saccharomyces cerevisiae Rad51 Paralogs in Sister Chromatid Recombination

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