title: A role for nuclear envelope-bridging complexes in homology-directed repair.
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.
authors.affiliation: Department of Cell Biology, Yale School of Medicine, New Haven, CT -06520.
authors.forename: Rebecca K
authors.initials: RK
authors.lastname: Swartz
authors.affiliation: Department of Cell Biology, Yale School of Medicine, New Haven, CT -06520.
authors.forename: Elisa C
authors.initials: EC
authors.lastname: Rodriguez
authors.affiliation: Department of Cell Biology, Yale School of Medicine, New Haven, CT -06520 megan.king@yale.edu.
authors.forename: Megan C
authors.initials: MC
authors.lastname: King
mesh_terms: D002453:Cell Cycle; D053903:DNA Breaks, Double-Stranded; D004260:DNA Repair; D004271:DNA, Fungal / Q000235:genetics; D004277:DNA, Single-Stranded / Q000235:genetics; D042822:Genomic Instability; D008870:Microtubules / Q000378:metabolism; D009685:Nuclear Envelope / Q000378:metabolism*; D012568:Schizosaccharomyces / Q000235:genetics* / Q000378:metabolism; D029702:Schizosaccharomyces pombe Proteins / Q000235:genetics / Q000378:metabolism*
chemical_list: D004271:DNA, Fungal; D004277:DNA, Single-Stranded; C105996:KMS1 protein, S pombe; C093512:SAD1 protein, S pombe; D029702:Schizosaccharomyces pombe Proteins