RRC ID 30732
著者 Swartz RK, Rodriguez EC, King MC.
タイトル A role for nuclear envelope-bridging complexes in homology-directed repair.
ジャーナル Mol Biol Cell
Abstract Unless efficiently and faithfully repaired, DNA double-strand breaks (DSBs) cause genome instability. We implicate a Schizosaccharomyces pombe nuclear envelope-spanning linker of nucleoskeleton and cytoskeleton (LINC) complex, composed of the Sad1/Unc84 protein Sad1 and Klarsicht/Anc1/SYNE1 homology protein Kms1, in the repair of DSBs. An induced DSB associates with Sad1 and Kms1 in S/G2 phases of the cell cycle, connecting the DSB to cytoplasmic microtubules. DSB resection to generate single-stranded DNA and the ATR kinase drive the formation of Sad1 foci in response to DNA damage. Depolymerization of microtubules or loss of Kms1 leads to an increase in the number and size of DSB-induced Sad1 foci. Further, Kms1 and the cytoplasmic microtubule regulator Mto1 promote the repair of an induced DSB by gene conversion, a type of homology-directed repair. kms1 genetically interacts with a number of genes involved in homology-directed repair; these same gene products appear to attenuate the formation or promote resolution of DSB-induced Sad1 foci. We suggest that the connection of DSBs with the cytoskeleton through the LINC complex may serve as an input to repair mechanism choice and efficiency.
巻・号 25(16)
ページ 2461-71
公開日 2014-8-15
DOI 10.1091/mbc.E13-10-0569
PII mbc.E13-10-0569
PMID 24943839
PMC PMC4142617
MeSH Cell Cycle DNA Breaks, Double-Stranded DNA Repair* DNA, Fungal / genetics DNA, Single-Stranded / genetics Genomic Instability Microtubules / metabolism Nuclear Envelope / metabolism* Schizosaccharomyces / genetics* Schizosaccharomyces / metabolism Schizosaccharomyces pombe Proteins / genetics Schizosaccharomyces pombe Proteins / metabolism*
IF 3.791
引用数 42
WOS 分野 CELL BIOLOGY
リソース情報
酵母 FY18394 FY18537