Identification and characterization of the rlp1+, the novel Rad51 paralog in the fission yeast Schizosaccharomyces pombe

Хасанов, Ф. К.; Salakhova, Albina F.; Chepurnaja, Olga V.; Korolev, V. G.; Bashkirov, Vladimir I.

doi:10.1016/j.dnarep.2004.05.010

Cited by 24 publications

(24 citation statements)

References 58 publications

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“…Cisplatin forms DNA adducts including ICLs that lead to replication fork breakage. As expected from previous studies, 38,39 HR (rad51D and rad52D) mutants were highly sensitive to CPT, HU, and cisplatin (Fig 4B), indicating the requirement of HR in repair of various types of DNA damage. However, NER mutants, swi9D and swi10D cells were not sensitive to CPT or HU but were highly sensitive to cisplatin (Fig 4B).…”

Section: Acetaldehyde Forms Dna Adducts That Are Removed By Nersupporting

confidence: 62%

Genetic controls of DNA damage avoidance in response to acetaldehyde in fission yeast

et al. 2016

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Acetaldehyde, a primary metabolite of alcohol, forms DNA adducts and disrupts the DNA replication process, causing genomic instability, a hallmark of cancer. Indeed, chronic alcohol consumption accounts for approximately 3.6% of all cancers worldwide. However, how the adducts are prevented and repaired after acetaldehyde exposure is not well understood. In this report, we used the fission yeast Schizosaccharomyces pombe as a model organism to comprehensively understand the genetic controls of DNA damage avoidance in response to acetaldehyde. We demonstrate that Atd1 functions as a major acetaldehyde detoxification enzyme that prevents accumulation of Rad52-DNA repair foci, while Atd2 and Atd3 have minor roles in acetaldehyde detoxification. We found that acetaldehyde causes DNA damage at the replication fork and activates the cell cycle checkpoint to coordinate cell cycle arrest with DNA repair. Our investigation suggests that acetaldehyde-mediated DNA adducts include interstrand-crosslinks and DNA-protein crosslinks. We also demonstrate that acetaldehyde activates multiple DNA repair pathways. Nucleotide excision repair and homologous recombination, which are both epistatically linked to the Fanconi anemia pathway, have major roles in acetaldehyde tolerance, while base excision repair and translesion synthesis also contribute to the prevention of acetaldehyde-dependent genomic instability. We also show the involvement of Wss1-related metalloproteases, Wss1 and Wss2, in acetaldehyde tolerance. These results indicate that acetaldehyde causes cellular stresses that require cells to coordinate multiple cellular processes in order to prevent genomic instability. Considering that acetaldehyde is a human carcinogen, our genetic studies serve as a guiding investigation into the mechanisms of acetaldehyde-dependent genomic instability and carcinogenesis.

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Section: Acetaldehyde Forms Dna Adducts That Are Removed By Nersupporting

confidence: 62%

Genetic controls of DNA damage avoidance in response to acetaldehyde in fission yeast

et al. 2016

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“…The detection of four Rad51 paralogs in Schizosaccharomyces pombe [Rhp55, Rhp57, Rlp1 (Khasanov et al 2004), and Rdl1 (Martin et al 2006)] and of Wve paralogs in vertebrates: Rad51B, Rad51C, Rad51D, XRCC2 and XRCC3 (Symington 2002;Thompson and Schild 2001), indicates a functional diversiWcation of RecA-like proteins during evolution. The exact mechanism of Rad51 paralog function is not known, but it is believed that they act by enhancing the nucleation or stabilization of the Rad51 nucleoprotein Wlament.…”

Section: Introductionmentioning

confidence: 99%

“…The exact mechanism of Rad51 paralog function is not known, but it is believed that they act by enhancing the nucleation or stabilization of the Rad51 nucleoprotein Wlament. Further homologs of the RAD52 group have been identiWed in S. pombe as well, including rad32 (MRE11 Sc ), rad50, nbs1 (XRS2 Sc ), rad51/rhp51 (RAD51 Sc ), rhp54 (RAD54 Sc ), rhp55 (RAD55 Sc ), rhp57 (RAD57 Sc ), rlp1 (novel rad51 paralog), rad22A and rti1/rad22B (RAD52 Sc and RAD59 Sc ) (Hartsuiker et al 2001;Khasanov et al 2004;Ueno et al 2003); Khasanov and Bashkirov 2001;Pastink et al 2001). Although the biochemistry of the corresponding proteins, including the RecA-like proteins Rad51, Rhp55, Rhp57, and Rlp1 has not been systematically studied, they are presumed to have similar properties like their S. cerevisiae counterparts.…”

Section: Introductionmentioning

confidence: 99%

“…The fbh1 gene encoding the F-box DNA helicase with a role in processing of recombination intermediates acts downstream of rad51 and rhp57 in a pathway of recombinational repair (Morishita et al 2005). The rlp1 (Khasanov et al 2004) and rdl1 (Martin et al 2006) genes encode two RecA-like proteins as nearest homologs of human XRCC2 and RAD51D. These proteins together with Sws1 form a complex that controls an early step of homologous recombination (Martin et al 2006).…”

Section: Introductionmentioning

confidence: 99%

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Genetic analysis reveals different roles of Schizosaccharomyces pombe sfr1/dds20 in meiotic and mitotic DNA recombination and repair

et al. 2008

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DNA double-strand break (DSB) repair mediated by the Rad51 pathway of homologous recombination is conserved in eukaryotes. In yeast, Rad51 paralogs, Saccharomyces cerevisiae Rad55-Rad57 and Schizosaccharomyces pombe Rhp55-Rhp57, are mediators of Rad51 nucleoprotein formation. The recently discovered S. pombe Sfr1/Dds20 protein has been shown to interact with Rad51 and to operate in the Rad51-dependent DSB repair pathway in parallel to the paralog-mediated pathway. Here we show that Sfr1 is a nuclear protein and acts downstream of Rad50 in DSB processing. sfr1 is epistatic to rad18 ¡ and rad60 ¡ , and Sfr1 is a high-copy suppressor of the replication and repair defects of a rad60 mutant. Sfr1 functions in a Cds1-independent UV damage tolerance mechanism. In contrast to mitotic recombination, meiotic recombination is signiWcantly reduced in sfr1 strains. Our data indicate that Sfr1 acts in DSB repair mainly outside of S-phase, and is required for wild-type levels of meiotic recombination. We suggest that Sfr1 acts early in recombination and has a speciWc role in Rad51 Wlament assembly, distinct from that of the Rad51 paralogs.

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“…In humans there are five of these paralogues, RAD51B-D and XRCC2-3, and in budding yeast there are four which form two distinct complexes, Rad55-Rad57 and Shu1-Psy3 (Heyer et al, 2010). The fission yeast, Schizosaccharomyces pombe, also possesses multiple Rad51 (Rhp51 in S. pombe) paralogues, along with an additional Rad51 mediator, Sws1, suggesting that their mechanisms of action are likely to be highly conserved (Grishchuk & Kohli, 2003;Khasanov et al, 2004;Martin et al, 2006). In addition to these Rad51 paralogues, fission yeast and mammalian cells have another pair of Rad51 mediators, Swi5 and Sfr1 (Akamatsu et al, 2003;Haruta et al, 2006;Khasanov et al, 2008;Akamatsu & Jasin, 2010).…”

Section: Strand Invasionmentioning

confidence: 99%

Eukaryote DNA Replication and Recombination: an Intimate Association

McFarlane¹,

Al-Zeer²,

Dalgaard³

2011

DNA Replication-Current Advances

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Identification and characterization of the rlp1+, the novel Rad51 paralog in the fission yeast Schizosaccharomyces pombe

Cited by 24 publications

References 58 publications

Genetic controls of DNA damage avoidance in response to acetaldehyde in fission yeast

Genetic controls of DNA damage avoidance in response to acetaldehyde in fission yeast

Genetic analysis reveals different roles of Schizosaccharomyces pombe sfr1/dds20 in meiotic and mitotic DNA recombination and repair

Eukaryote DNA Replication and Recombination: an Intimate Association

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