RRC ID 53377
Author Lawrence KS, Tapley EC, Cruz VE, Li Q, Aung K, Hart KC, Schwartz TU, Starr DA, Engebrecht J.
Title LINC complexes promote homologous recombination in part through inhibition of nonhomologous end joining.
Journal J Cell Biol
Abstract The Caenorhabditis elegans SUN domain protein, UNC-84, functions in nuclear migration and anchorage in the soma. We discovered a novel role for UNC-84 in DNA damage repair and meiotic recombination. Loss of UNC-84 leads to defects in the loading and disassembly of the recombinase RAD-51. Similar to mutations in Fanconi anemia (FA) genes, unc-84 mutants and human cells depleted of Sun-1 are sensitive to DNA cross-linking agents, and sensitivity is rescued by the inactivation of nonhomologous end joining (NHEJ). UNC-84 also recruits FA nuclease FAN-1 to the nucleoplasm, suggesting that UNC-84 both alters the extent of repair by NHEJ and promotes the processing of cross-links by FAN-1. UNC-84 interacts with the KASH protein ZYG-12 for DNA damage repair. Furthermore, the microtubule network and interaction with the nucleoskeleton are important for repair, suggesting that a functional linker of nucleoskeleton and cytoskeleton (LINC) complex is required. We propose that LINC complexes serve a conserved role in DNA repair through both the inhibition of NHEJ and the promotion of homologous recombination at sites of chromosomal breaks.
Volume 215(6)
Pages 801-821
Published 2016-12-19
DOI 10.1083/jcb.201604112
PII jcb.201604112
PMID 27956467
PMC PMC5166498
MeSH Caenorhabditis elegans Proteins / metabolism* Cell Cycle Checkpoints / drug effects Cell Cycle Checkpoints / radiation effects Cell Nucleus / drug effects Cell Nucleus / metabolism Cell Nucleus / radiation effects Cell Proliferation / drug effects Cell Proliferation / radiation effects Cisplatin / pharmacology Cross-Linking Reagents / metabolism DNA Damage DNA End-Joining Repair* / drug effects DNA End-Joining Repair* / radiation effects Germ Cells / cytology Germ Cells / drug effects Germ Cells / metabolism Germ Cells / radiation effects Homologous Recombination* / drug effects Homologous Recombination* / radiation effects Humans Hydroxyurea / pharmacology Meiosis / drug effects Meiosis / radiation effects Membrane Proteins / metabolism Microtubule-Associated Proteins / metabolism Microtubules / drug effects Microtubules / metabolism Microtubules / radiation effects Models, Biological Multiprotein Complexes / metabolism* Nuclear Proteins / metabolism Polymerization / drug effects Protein Binding / drug effects Protein Binding / radiation effects Protein Transport / drug effects Protein Transport / radiation effects Radiation, Ionizing
IF 8.811
Times Cited 19
C.elegans tm1524 tm1145 tm1268 tm423