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.
© 2016 Lawrence et al.
MeSH terms
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Caenorhabditis elegans Proteins / metabolism*
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Cell Cycle Checkpoints / drug effects
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Cell Cycle Checkpoints / radiation effects
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Cell Nucleus / drug effects
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Cell Nucleus / metabolism
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Cell Nucleus / radiation effects
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Cell Proliferation / drug effects
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Cell Proliferation / radiation effects
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Cisplatin / pharmacology
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Cross-Linking Reagents / metabolism
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DNA Damage
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DNA End-Joining Repair* / drug effects
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DNA End-Joining Repair* / radiation effects
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Germ Cells / cytology
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Germ Cells / drug effects
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Germ Cells / metabolism
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Germ Cells / radiation effects
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Homologous Recombination* / drug effects
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Homologous Recombination* / radiation effects
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Humans
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Hydroxyurea / pharmacology
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Meiosis / drug effects
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Meiosis / radiation effects
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Membrane Proteins / metabolism
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Microtubule-Associated Proteins / metabolism
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Microtubules / drug effects
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Microtubules / metabolism
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Microtubules / radiation effects
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Models, Biological
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Multiprotein Complexes / metabolism*
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Nuclear Proteins / metabolism
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Polymerization / drug effects
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Protein Binding / drug effects
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Protein Binding / radiation effects
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Protein Transport / drug effects
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Protein Transport / radiation effects
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Radiation, Ionizing
Substances
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Caenorhabditis elegans Proteins
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Cross-Linking Reagents
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Membrane Proteins
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Microtubule-Associated Proteins
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Multiprotein Complexes
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Nuclear Proteins
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SUN1 protein, human
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Cisplatin
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Hydroxyurea