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A role for nuclear envelope–bridging complexes in homology-directed repair

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...

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Autores principales: Swartz, Rebecca K., Rodriguez, Elisa C., King, Megan C.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: The American Society for Cell Biology 2014
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4142617/
https://www.ncbi.nlm.nih.gov/pubmed/24943839
http://dx.doi.org/10.1091/mbc.E13-10-0569
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author Swartz, Rebecca K.
Rodriguez, Elisa C.
King, Megan C.
author_facet Swartz, Rebecca K.
Rodriguez, Elisa C.
King, Megan C.
author_sort Swartz, Rebecca K.
collection PubMed
description 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.
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spelling pubmed-41426172014-10-30 A role for nuclear envelope–bridging complexes in homology-directed repair Swartz, Rebecca K. Rodriguez, Elisa C. King, Megan C. Mol Biol Cell Articles 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. The American Society for Cell Biology 2014-08-15 /pmc/articles/PMC4142617/ /pubmed/24943839 http://dx.doi.org/10.1091/mbc.E13-10-0569 Text en © 2014 Swartz et al. This article is distributed by The American Society for Cell Biology under license from the author(s). Two months after publication it is available to the public under an Attribution–Noncommercial–Share Alike 3.0 Unported Creative Commons License (http://creativecommons.org/licenses/by-nc-sa/3.0). “ASCB®,” “The American Society for Cell Biology®,” and “Molecular Biology of the Cell®” are registered trademarks of The American Society of Cell Biology.
spellingShingle Articles
Swartz, Rebecca K.
Rodriguez, Elisa C.
King, Megan C.
A role for nuclear envelope–bridging complexes in homology-directed repair
title A role for nuclear envelope–bridging complexes in homology-directed repair
title_full A role for nuclear envelope–bridging complexes in homology-directed repair
title_fullStr A role for nuclear envelope–bridging complexes in homology-directed repair
title_full_unstemmed A role for nuclear envelope–bridging complexes in homology-directed repair
title_short A role for nuclear envelope–bridging complexes in homology-directed repair
title_sort role for nuclear envelope–bridging complexes in homology-directed repair
topic Articles
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4142617/
https://www.ncbi.nlm.nih.gov/pubmed/24943839
http://dx.doi.org/10.1091/mbc.E13-10-0569
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