title: LINC complexes promote homologous recombination in part through inhibition of nonhomologous end joining.
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.
authors.affiliation: Department of Molecular and Cellular Biology; Biochemistry, Molecular Cellular, and Developmental Biology Graduate Group, University of California, Davis, Davis, CA 95616.
authors.forename: Katherine S
authors.initials: KS
authors.lastname: Lawrence
authors.affiliation: Department of Molecular and Cellular Biology; Biochemistry, Molecular Cellular, and Developmental Biology Graduate Group, University of California, Davis, Davis, CA 95616.
authors.forename: Erin C
authors.initials: EC
authors.lastname: Tapley
authors.affiliation: Department of Biology, Massachusetts Institute of Technology, Cambridge, MA 02139.
authors.forename: Victor E
authors.identifier: http://orcid.org/0000-0001-5338-0973
authors.initials: VE
authors.lastname: Cruz
authors.affiliation: Department of Molecular and Cellular Biology; Biochemistry, Molecular Cellular, and Developmental Biology Graduate Group, University of California, Davis, Davis, CA 95616.
authors.forename: Qianyan
authors.initials: Q
authors.lastname: Li
authors.affiliation: Department of Molecular and Cellular Biology; Biochemistry, Molecular Cellular, and Developmental Biology Graduate Group, University of California, Davis, Davis, CA 95616.
authors.forename: Kayla
authors.initials: K
authors.lastname: Aung
authors.affiliation: Department of Molecular and Cellular Biology; Biochemistry, Molecular Cellular, and Developmental Biology Graduate Group, University of California, Davis, Davis, CA 95616.
authors.forename: Kevin C
authors.initials: KC
authors.lastname: Hart
authors.affiliation: Department of Biology, Massachusetts Institute of Technology, Cambridge, MA 02139.
authors.forename: Thomas U
authors.identifier: http://orcid.org/0000-0001-8012-1512
authors.initials: TU
authors.lastname: Schwartz
authors.affiliation: Department of Molecular and Cellular Biology; Biochemistry, Molecular Cellular, and Developmental Biology Graduate Group, University of California, Davis, Davis, CA 95616 jengebrecht@ucdavis.edu dastarr@ucdavis.edu.
authors.forename: Daniel A
authors.initials: DA
authors.lastname: Starr
authors.affiliation: Department of Molecular and Cellular Biology; Biochemistry, Molecular Cellular, and Developmental Biology Graduate Group, University of California, Davis, Davis, CA 95616 jengebrecht@ucdavis.edu dastarr@ucdavis.edu.
authors.forename: JoAnne
authors.identifier: http://orcid.org/0000-0002-2733-7506
authors.initials: J
authors.lastname: Engebrecht
mesh_terms: D029742:Caenorhabditis elegans Proteins / Q000378:metabolism*; D059447:Cell Cycle Checkpoints / Q000187:drug effects / Q000528:radiation effects; D002467:Cell Nucleus / Q000187:drug effects / Q000378:metabolism / Q000528:radiation effects; D049109:Cell Proliferation / Q000187:drug effects / Q000528:radiation effects; D002945:Cisplatin / Q000494:pharmacology; D003432:Cross-Linking Reagents / Q000378:metabolism; D004249:DNA Damage; D059766:DNA End-Joining Repair / Q000187:drug effects / Q000528:radiation effects; D005854:Germ Cells / Q000166:cytology / Q000187:drug effects / Q000378:metabolism / Q000528:radiation effects; D059765:Homologous Recombination / Q000187:drug effects / Q000528:radiation effects; D006801:Humans; D006918:Hydroxyurea / Q000494:pharmacology; D008540:Meiosis / Q000187:drug effects / Q000528:radiation effects; D008565:Membrane Proteins / Q000378:metabolism; D008869:Microtubule-Associated Proteins / Q000378:metabolism; D008870:Microtubules / Q000187:drug effects / Q000378:metabolism / Q000528:radiation effects; D008954:Models, Biological; D046912:Multiprotein Complexes / Q000378:metabolism*; D009687:Nuclear Proteins / Q000378:metabolism; D058105:Polymerization / Q000187:drug effects; D011485:Protein Binding / Q000187:drug effects / Q000528:radiation effects; D021381:Protein Transport / Q000187:drug effects / Q000528:radiation effects; D011839:Radiation, Ionizing
chemical_list: D029742:Caenorhabditis elegans Proteins; D003432:Cross-Linking Reagents; D008565:Membrane Proteins; D008869:Microtubule-Associated Proteins; D046912:Multiprotein Complexes; D009687:Nuclear Proteins; C506117:SUN1 protein, human; D002945:Cisplatin; D006918:Hydroxyurea