LINC complexes promote homologous recombination in part through inhibition of nonhomologous end joining
Name
Lawrence-2016-LINC complexes promote homologou.pdf
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3.27 MB
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Author(s)
Lawrence, Katherine S.
Tapley, Erin C.
Cruz, Victor E.
Li, Qianyan
Aung, Kayla
Hart, Kevin C.
Starr, Daniel A.
Engebrecht, JoAnne
Schwartz, Thomas
Date Issued
December 2016
Journal
The Journal of Cell Biology
Publisher
Rockefeller University Press
Citation
Lawrence, Katherine S. et al. “LINC Complexes Promote Homologous Recombination in Part through Inhibition of Nonhomologous End Joining.” The Journal of Cell Biology 215.6 (2016): 801–821.
Version
Final published version
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.
MIT Department
Massachusetts Institute of Technology. Department of Biology
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Creative Commons Attribution-Noncommercial-Share Alike
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DOI of Published Version
https://doi.org/10.1083/jcb.201604112
