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

被引:0
|
作者
Baranowska, Gabriela [1 ]
Misiorna, Dorota [1 ]
Bialek, Wojciech [1 ]
Kramarz, Karol [2 ]
Dziadkowiec, Dorota [1 ]
机构
[1] Univ Wroclaw, Fac Biotechnol, Wroclaw, Poland
[2] Univ Wroclaw, Fac Biol Sci, Res Ctr DNA Repair & Replicat, Acad Excellence Hub, Wroclaw, Poland
来源
PLOS ONE | 2024年 / 19卷 / 06期
关键词
HOMOLOGOUS RECOMBINATION; REPAIR; DAMAGE; RAD51; INVOLVEMENT; GENOME;
D O I
10.1371/journal.pone.0300434
中图分类号
O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];
学科分类号
07 ; 0710 ; 09 ;
摘要
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. Using Schizosaccharomyces pombe we 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. We demonstrate that Srs2 localises to rDNA region and is required for proper replication of rDNA arrays. 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. On the other hand, upregulation of Rrp2 primarily leads to replication stress response checkpoint activation. Overall, we propose that Srs2, Rrp1 and Rrp2 have important and at least partially independent functions in the maintenance of distinct difficult to replicate regions of the genome.
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页数:19
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