RRC ID 47910
著者 Manjón E, Edreira T, Muñoz S, Sánchez Y.
タイトル Rgf1p (Rho1p GEF) is required for double-strand break repair in fission yeast.
ジャーナル Nucleic Acids Res
Abstract Rho GTPases are conserved molecules that control cytoskeletal dynamics. These functions are expedited by Rho GEFs that stimulate the release of GDP to enable GTP binding, thereby allowing Rho proteins to initiate intracellular signaling. How Rho GEFs and Rho GTPases protect cells from DNA damage is unknown. Here, we explore the extreme sensitivity of a deletion mutation in the Rho1p exchange factor Rgf1p to the DNA break/inducing antibiotic phleomycin (Phl). The Rgf1p mutant cells are defective in reentry into the cell cycle following the induction of severe DNA damage. This phenotype correlates with the inability of rgf1Δ cells to efficiently repair fragmented chromosomes after Phl treatment. Consistent with this observation Rad11p (ssDNA binding protein, RPA), Rad52p, Rad54p and Rad51p, which facilitate strand invasion in the process of homology-directed repair (HDR), are permanently stacked in Phl-induced foci in rgf1Δ cells. These phenotypes are phenocopied by genetic inhibition of Rho1p. Our data provide evidence that Rgf1p/Rho1p activity positively controls a repair function that confers resistance against the anti-cancer drug Phl.
巻・号 45(9)
ページ 5269-5284
公開日 2017-5-19
DOI 10.1093/nar/gkx176
PII 3071711
PMID 28334931
PMC PMC5435928
MeSH Chromosomes, Fungal / genetics DNA Breaks, Double-Stranded* / drug effects DNA Repair* / drug effects G2 Phase Cell Cycle Checkpoints / drug effects Green Fluorescent Proteins / metabolism Guanine Nucleotide Exchange Factors / metabolism* Homologous Recombination / drug effects Microbial Viability / drug effects Mutation / genetics Phleomycins / pharmacology Schizosaccharomyces / drug effects Schizosaccharomyces / metabolism* Schizosaccharomyces pombe Proteins / metabolism* Signal Transduction / drug effects
IF 11.502
引用数 0
WOS 分野 BIOCHEMISTRY & MOLECULAR BIOLOGY
リソース情報
酵母 FY14080