Redundant roles of Srs2 helicase and replication checkpoint in survival and rDNA maintenance in Schizosaccharomyces pombe

Yasuhira, Shinji

doi:10.1007/s00438-009-0426-x

Cited by 11 publications

(16 citation statements)

References 60 publications

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“…Srs2 has been shown to work in a pathway redundant to Rad3 and Mrc1, possibly independent from checkpoint signalling functions of these proteins but requiring Srs2 ATPase activity [20]. Consistently, we observed that the double chk1Δsrs2Δ mutant was more sensitive to HU and CPT than single chk1Δ mutant (Fig.…”

Section: Differential Checkpoint Activation By Upregulation Of Srs2 R...supporting

confidence: 87%

Replication stress response in fission yeast differentially depends on maintaining proper levels of Srs2 helicase and Rrp1, Rrp2 DNA translocases

Baranowska,

Misiorna,

Białek

et al. 2023

Preprint

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Homologous recombination is a key process that governs the stability of eukaryotic genomes during DNA replication and repair. Multiple auxiliary factors regulate the choice of homologous recombination pathway in response to different types of replication stress. UsingSchizosaccharomyces pombewe have previously suggested the role of DNA translocases Rrp1 and Rrp2, together with Srs2 helicase, in the common synthesis dependent strand annealing sub-pathway of homologous recombination. Here we show that all three proteins are important for completion of replication after hydroxyurea exposure and provide data comparing the effect of overproduction of Srs2 with Rrp1 and Rrp2. Upregulation of Srs2 protein levels leads to enhanced replication stress, chromosome instability and viability loss, as previously reported for Rrp1 and Rrp2. Interestingly, our data suggests that dysregulation of Srs2, Rrp1 and Rrp2 protein levels differentially affects checkpoint response. Overproduction of Srs2 activates simultaneously DNA damage and replication stress response checkpoints, while cells overproducing Rrp1 mainly launch DNA damage checkpoint. Upregulation of Rrp2 primarily leads to replication stress response checkpoint activation. Overall, we propose that Srs2, Rrp1 and Rrp2 have important and independent functions for maintenance of distinct difficult to replicate regions of the genome.

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Section: Differential Checkpoint Activation By Upregulation Of Srs2 R...supporting

confidence: 87%

Replication stress response in fission yeast differentially depends on maintaining proper levels of Srs2 helicase and Rrp1, Rrp2 DNA translocases

Baranowska,

Misiorna,

Białek

et al. 2023

Preprint

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“…Srs2 helicase appears to have additional roles at the replication checkpoint that may be independent of HR (Yasuhira 2009). srs2 mutants are defective in activation of the DNA damage response (Liberi et al 2000), allowing lethal recombination intermediates to form.…”

Section: Srs2 In Replicationmentioning

confidence: 99%

Multifunctional Roles of Saccharomyces cerevisiae Srs2 protein in Replication, Recombination and Repair

Niu

Klein

2016

FEMS Yeast Research

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One sentence summary: Srs2 is a multifunctional protein that acts during cell replication to insure faithful and accurate copying of genetic information. Editor: Uffe Mortensen ABSTRACTThe Saccharomyces cerevisiae Srs2 DNA helicase has important roles in DNA replication, recombination and repair. In replication, Srs2 aids in repair of gaps by repair synthesis by preventing gaps from being used to initiate recombination. This is considered to be an anti-recombination role. In recombination, Srs2 plays both prorecombination and anti-recombination roles to promote the synthesis-dependent strand annealing recombination pathway and to inhibit gaps from initiating homologous recombination. In repair, the Srs2 helicase actively promotes gap repair through an interaction with the Exo1 nuclease to enlarge a gap for repair and to prevent Rad51 protein from accumulating on single-stranded DNA. Finally, Srs2 helicase can unwind hairpin-forming repeat sequences to promote replication and prevent repeat instability. The Srs2 activities can be controlled by phosphorylation, SUMO modification and interaction with key partners at DNA damage or lesions sites, which include PCNA and Rad51. These interactions can also limit DNA polymerase function during recombinational repair independent of the Srs2 translocase or helicase activity, further highlighting the importance of the Srs2 protein in regulating recombination. Here we review the myriad roles of Srs2 that have been documented in genome maintenance and distinguish between the translocase, helicase and additional functions of the Srs2 protein.

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“…However, mechanistic interpretation of the molecular defects underlying srs2Δ phenotypes are complicated by the fact that Srs2 also participates in HR-independent processes related to genome integrity (reviewed in refs. 16 and 27), in particular with respect to replication through DNA secondary structure (28)(29)(30), replication checkpoint activation (31,32), preventing ssDNA gaps present at stalled replication forks from being used to initiate recombination (33,34), and Top1-mediated removal of misincorporated ribonucleotides (35).…”

mentioning

confidence: 99%

Meiosis-specific recombinase Dmc1 is a potent inhibitor of the Srs2 antirecombinase

Crickard

Kaniecki

Kwon

et al. 2018

Proc. Natl. Acad. Sci. U.S.A.

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Cross-over recombination products are a hallmark of meiosis because they are necessary for accurate chromosome segregation and they also allow for increased genetic diversity during sexual reproduction. However, cross-overs can also cause gross chromosomal rearrangements and are therefore normally down-regulated during mitotic growth. The mechanisms that enhance cross-over product formation upon entry into meiosis remain poorly understood. In Saccharomyces cerevisiae, the Superfamily 1 (Sf1) helicase Srs2, which is an ATP hydrolysis-dependent motor protein that actively dismantles recombination intermediates, promotes synthesisdependent strand annealing, the result of which is a reduction in cross-over recombination products. Here, we show that the meiosisspecific recombinase Dmc1 is a potent inhibitor of Srs2. Biochemical and single-molecule assays demonstrate that Dmc1 acts by inhibiting Srs2 ATP hydrolysis activity, which prevents the motor protein from undergoing ATP hydrolysis-dependent translocation on Dmc1bound recombination intermediates. We propose a model in which Dmc1 helps contribute to cross-over formation during meiosis by antagonizing the antirecombinase activity of Srs2.

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Redundant roles of Srs2 helicase and replication checkpoint in survival and rDNA maintenance in Schizosaccharomyces pombe

Cited by 11 publications

References 60 publications

Replication stress response in fission yeast differentially depends on maintaining proper levels of Srs2 helicase and Rrp1, Rrp2 DNA translocases

Replication stress response in fission yeast differentially depends on maintaining proper levels of Srs2 helicase and Rrp1, Rrp2 DNA translocases

Multifunctional Roles of Saccharomyces cerevisiae Srs2 protein in Replication, Recombination and Repair

Meiosis-specific recombinase Dmc1 is a potent inhibitor of the Srs2 antirecombinase

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