The Rad52 Homologs Rad22 and Rti1 of<i>Schizosaccharomyces pombe</i>Are Not Essential for Meiotic Interhomolog Recombination, but Are Required for Meiotic Intrachromosomal Recombination and Mating-Type-Related DNA Repair

Octobre, Guillaume; Lorenz, Alexander; Loidl, Josef; Kohli, Jürg

doi:10.1534/genetics.107.085696

Cited by 25 publications

(38 citation statements)

References 82 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…This indicates that the large majority of meiotic intrachromosomal events in the wild type derive from DSBs formed by Rec12. It had been shown before that deletion of the S. pombe RAD52 homologs rad22 and rti1 affected recombination between homologous chromosomes only slightly (maximal 2.5-fold reduction) but reduced prototroph formation in the PS1 assay 80-fold (50). In the VL1 assay the ppm reductions were 7-fold (rad22⌬), 1.9-fold (rti1⌬), and 14-fold (rad22⌬ rti1⌬).…”

Section: Hop1 and Mek1 Proteins Contribute To Homologous Pairingmentioning

confidence: 90%

“…In S. pombe loss of core HR functions leads to very low spore viability: deletion of rad51 but not of dmc1 (20), double mutation of rad54 and rdh54 (7), inactivation of the endonuclease activity encoded by mus81 and eme1 (5,52), and combined deletion of rad22 and rti1 (homologs of RAD52 of S. cerevisiae). But, differently from the other core functions, Rad22 and Rti1 are not required for CO and NCO (50).…”

mentioning

confidence: 99%

See 1 more Smart Citation

Roles of Hop1 and Mek1 in Meiotic Chromosome Pairing and Recombination Partner Choice in Schizosaccharomyces pombe

Latypov

Rothenberg

Lorenz

et al. 2010

Molecular and Cellular Biology

Self Cite

View full text Add to dashboard Cite

Synaptonemal complex (SC) proteins Hop1 and Mek1 have been proposed to promote homologous recombination in meiosis of Saccharomyces cerevisiae by establishment of a barrier against sister chromatid recombination. Therefore, it is interesting to know whether the homologous proteins play a similar role in Schizosaccharomyces pombe. Unequal sister chromatid recombination (USCR) was found to be increased in hop1 and mek1 single and double deletion mutants in assays for intrachromosomal recombination (ICR). Meiotic intergenic (crossover) and intragenic (conversion) recombination between homologous chromosomes was reduced. Double-strand break (DSB) levels were also lowered. Notably, deletion of hop1 restored DSB repair in rad50S meiosis. This may indicate altered DSB repair kinetics in hop1 and mek1 deletion strains. A hypothesis is advanced proposing transient inhibition of DSB processing by Hop1 and Mek1 and thus providing more time for repair by interaction with the homologous chromosome. Loss of Hop1 and Mek1 would then result in faster repair and more interaction with the sister chromatid. Thus, in S. pombe meiosis, where an excess of sister Holliday junction over homologous Holliday junction formation has been demonstrated, Hop1 and Mek1 possibly enhance homolog interactions to ensure wild-type level of crossover formation rather than inhibiting sister chromatid interactions.Sexual reproduction in eukaryotes involves formation of haploid gametes from diploid cells by one round of DNA replication, pairing of the homologous chromosomes, and recombination and then by the two meiotic divisions (53). In fungi the gametes differentiate into haploid spores, which germinate to form vegetative cells. Crossover (CO) formation between homologous chromosomes and DNA repair processes between sister chromatids are required for spore viability (10,55,58).In vegetative cells homologous recombination (HR) is important for repair of DNA damage and stalled replication forks, with the sister chromatid as the preferred partner (28). Many of the enzymes involved in mitotic HR also contribute to meiotic recombination. In addition, meiosis-specific cytological structures and enzymes enhance recombination frequency (meiotic induction) and shift partner preference from sister chromatids to homologous chromosomes (3,47,64,74). In detail the steps of HR vary between different types of sequence organization (allelic versus sister versus ectopic), between different types of DNA damage, between meiotic and mitotic cells, and between species (10, 55, 58).Meiotic recombination, including CO formation, is initiated by DNA double-strand breaks (DSBs). In Saccharomyces cerevisiae and other eukaryotes, DSBs are formed by Spo11. Many cofactors are required (29). The Schizosaccharomyces pombe homolog is Rec12, also requiring auxiliary factors whose elimination leads to loss of meiotic DSB formation (12). The 5Ј single-strand ends at DSBs are processed by nucleases. In S. cerevisiae the MRX complex made up by the proteins Rad50, Mre11, and Xrs2 is req...

show abstract

Section: Hop1 and Mek1 Proteins Contribute To Homologous Pairingmentioning

confidence: 90%

mentioning

confidence: 99%

Roles of Hop1 and Mek1 in Meiotic Chromosome Pairing and Recombination Partner Choice in Schizosaccharomyces pombe

Latypov

Rothenberg

Lorenz

et al. 2010

Molecular and Cellular Biology

Self Cite

View full text Add to dashboard Cite

show abstract

“…Rad55 and Rad57 play a minor role in both interhomolog and intrasister exchanges at DSB-poor regions, while Rad52/Rti1 are implicated primarily in intrasister events (Akamatsu et al 2003;Octobre et al 2008;Hyppa and Smith 2010). We constructed double mutants to investigate whether rad16-249 could be placed genetically in either of these pathways.…”

Section: Xpf Required For Meiosis and Genome Stability 1463mentioning

confidence: 99%

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

Mastro¹,

Forsburg

2014

Genetics

View full text Add to dashboard Cite

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...

show abstract

“…In addition, our data indicate that Rad22 plays a negative regulatory role in Dmc1-driven strand exchange in contrast to its well-known positive role in Rad51-driven HR. Octobre et al (2008) have shown that Rad22 promotes intersister HR during meiosis in S. pombe and is not required for the production of interhomolog crossover recombinants. On the other hand, interhomolog recombinants are generated from DSB-cold regions in a Dmc1-dependent manner (Hyppa and Smith 2010).…”

Section: Discussionmentioning

confidence: 99%

“…Thus, Rad22 plays dual roles in regulating meiotic recombination: activating Rad51 and inhibiting Dmc1. Rad22 is important during meiosis in S. pombe for intersister HR, which leads to noncrossover recombinants, presumably by promoting DNA double-strand break (DSB) repair (Cromie et al 2006;Octobre et al 2008). On the other hand, crossover recombinants (i.e., via interhomolog HR) are produced from DSB-cold regions in a Dmc1-dependent manner (Hyppa and Smith 2010).…”

mentioning

confidence: 99%

Dual regulation of Dmc1-driven DNA strand exchange by Swi5–Sfr1 activation and Rad22 inhibition

Murayama¹,

Kurokawa²,

Tsutsui³

et al. 2013

Genes Dev.

View full text Add to dashboard Cite

Both ubiquitously expressed Rad51 and meiosis-specific Dmc1 are required for crossover production during meiotic recombination. The budding yeast Rad52 and its fission yeast ortholog, Rad22, are “mediators;” i.e., they help load Rad51 onto ssDNA coated with replication protein A (RPA). Here we show that the Swi5–Sfr1 complex from fission yeast is both a mediator that loads Dmc1 onto ssDNA and a direct “activator” of DNA strand exchange by Dmc1. In stark contrast, Rad22 inhibits Dmc1 action by competing for its binding to RPA-coated ssDNA. Thus, Rad22 plays dual roles in regulating meiotic recombination: activating Rad51 and inhibiting Dmc1.

show abstract

The Rad52 Homologs Rad22 and Rti1 ofSchizosaccharomyces pombeAre Not Essential for Meiotic Interhomolog Recombination, but Are Required for Meiotic Intrachromosomal Recombination and Mating-Type-Related DNA Repair

Cited by 25 publications

References 82 publications

Roles of Hop1 and Mek1 in Meiotic Chromosome Pairing and Recombination Partner Choice in Schizosaccharomyces pombe

Roles of Hop1 and Mek1 in Meiotic Chromosome Pairing and Recombination Partner Choice in Schizosaccharomyces pombe

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

Dual regulation of Dmc1-driven DNA strand exchange by Swi5–Sfr1 activation and Rad22 inhibition

Contact Info

Product

Resources

About