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

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.

Rrp1, Rrp2 and Uls1 - Yeast SWI2/SNF2 DNA dependent translocases in genome stability maintenance.

Multiple eukaryotic SWI2/SNF2 DNA translocases safeguard genome integrity, mostly by remodelling nucleosomes, but also by fine-tuning mechanisms of DNA repair, such as homologous recombination. Among this large family there is a unique class of Rad5/16-like enzymes, including Saccharomyces cerevisiae Uls1 and its Schizosaccharomyces pombe orthologues Rrp1 and Rrp2, that have both translocase and E3 ubiquitin ligase activities, and are often directed towards their substrates by SUMOylation. Here we summarize recent advances in understanding how different activities of these yeast proteins jointly contribute to their important roles in replication stress response particularly at centromeres and telomeres.

Rrp1 translocase and ubiquitin ligase activities restrict the genome destabilising effects of Rad51 in fission yeast.

Rad51 is the key protein in homologous recombination that plays important roles during DNA replication and repair. Auxiliary factors regulate Rad51 activity to facilitate productive recombination, and prevent inappropriate, untimely or excessive events, which could lead to genome instability. Previous genetic analyses identified a function for Rrp1 (a member of the Rad5/16-like group of SWI2/SNF2 translocases) in modulating Rad51 function, shared with the Rad51 mediator Swi5-Sfr1 and the Srs2 anti-recombinase.

DNA translocases Rrp1 and Rrp2 have distinct roles at centromeres and telomeres that ensure genome stability.

The regulation of telomere and centromere structure and function is essential for maintaining genome integrity. Rrp1 and Rrp2 are orthologues of Uls1, a SWI2/SNF2 DNA translocase and SUMO-targeted ubiquitin ligase. Here, we show that Rrp1 or Rrp2 overproduction leads to chromosome instability and growth defects, a reduction in global histone levels and mislocalisation of centromere-specific histone Cnp1.

DNA Damage Tolerance Pathway Choice Through Uls1 Modulation of Srs2 SUMOylation in .

DNA damage tolerance and homologous recombination pathways function to bypass replication-blocking lesions and ensure completion of DNA replication. However, inappropriate activation of these pathways may lead to increased mutagenesis or formation of deleterious recombination intermediates, often leading to cell death or cancer formation in higher organisms. Post-translational modifications of PCNA regulate the choice of repair pathways at replication forks.