Sfh1, an essential component of the RSC chromatin remodeling complex, maintains genome integrity in fission yeast

• Published in: Genes to cells : devoted to molecular & cellular mechanisms 2018-09, Vol.23 (9), p.738-752
• Main Authors: Kotomura, Naoe, Tsunemine, Satoru, Kuragano, Masahiro, Asanuma, Takahiro, Nakagawa, Hiromi, Tanaka, Katsunori, Murakami, Yota
• Format: Article
• Language: English
• Subjects: Cell Cycle Proteins - genetics; Cell Cycle Proteins - metabolism; Centromere; Chromatin Assembly and Disassembly; Chromatin remodeling; Chromosomal Proteins, Non-Histone - genetics; Chromosomal Proteins, Non-Histone - metabolism; Chromosome Segregation; Cohesin; Cohesins; DNA damage; Gene Expression Regulation, Fungal; Genomes; Genomic Instability; Heterochromatin; Homologous recombination; Homologous recombination repair; Mediator protein; Mutation; Rad52 protein; Retroelements; Schizosaccharomyces - genetics; Schizosaccharomyces pombe Proteins - genetics; Schizosaccharomyces pombe Proteins - metabolism; Ultraviolet radiation; Yeast
• ISSN: 1356-9597; 1365-2443
• DOI: 10.1111/gtc.12629

Abp1 is a fission yeast CENP‐B homologue that contributes to centromere function, silencing at pericentromeric heterochromatin and silencing of retrotransposons. We identified the sfh1 gene, encoding a core subunit of the fission yeast chromatin remodeling complex RSC as an Abp1‐interacting protein. Because sfh1 is essential for growth, we isolated temperature‐sensitive sfh1 mutants. These mutants showed defects in centromere functions, reflected by sensitivity to an inhibitor of spindle formation and minichromosome instability. Sfh1 localized at both kinetochore and pericentromeric heterochromatin regions. Although sfh1 mutations had minor effect on silencing at these regions, they decreased the levels of cohesin on centromeric heterochromatin. Sfh1 also localized at a retrotransposon, Tf2, in a partly Abp1‐dependent manner, and assisted in silencing of Tf2 by Abp1 probably in the same pathway as a histone chaperon, HIRA, which is also known to involve in Tf2 repression. Furthermore, sfh1 mutants were sensitive to several DNA‐damaging treatments (HU, MMS, UV and X‐ray). Increase in spontaneous foci of Rad22, a recombination Mediator protein Rad52 homologue, in sfh1 mutant suggests that RSC functions in homologous recombination repair of double‐stranded break downstream of the Rad22 recruitment. These results indicate that RSC plays multiple roles in the maintenance of genome integrity. We isolated Sfh1, an essential component of chromatin remodeler RSC, as a binding protein of CENP‐B homologue Abp1. Analysis of temperature‐sensitive mutant of Sfh1 showed that Sfh1/RSC involved in double‐strand DNA break repair, cohesin loading at pericetromere and repression of retrotransposons, which shows Sfh1/RSC plays an important role to maintain genome integrity.