53BP1 and the LINC Complex Promote Microtubule-Dependent DSB Mobility and DNA Repair.
Cell
; 163(4): 880-93, 2015 Nov 05.
Article
em En
| MEDLINE
| ID: mdl-26544937
Increased mobility of chromatin surrounding double-strand breaks (DSBs) has been noted in yeast and mammalian cells but the underlying mechanism and its contribution to DSB repair remain unclear. Here, we use a telomere-based system to track DNA damage foci with high resolution in living cells. We find that the greater mobility of damaged chromatin requires 53BP1, SUN1/2 in the linker of the nucleoskeleton, and cytoskeleton (LINC) complex and dynamic microtubules. The data further demonstrate that the excursions promote non-homologous end joining of dysfunctional telomeres and implicated Nesprin-4 and kinesins in telomere fusion. 53BP1/LINC/microtubule-dependent mobility is also evident at irradiation-induced DSBs and contributes to the mis-rejoining of drug-induced DSBs in BRCA1-deficient cells showing that DSB mobility can be detrimental in cells with numerous DSBs. In contrast, under physiological conditions where cells have only one or a few lesions, DSB mobility is proposed to prevent errors in DNA repair.
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Proteínas Cromossômicas não Histona
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Proteínas de Ligação a DNA
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Reparo do DNA
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Quebras de DNA de Cadeia Dupla
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Microtúbulos
Limite:
Animals
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Humans
Idioma:
En
Ano de publicação:
2015
Tipo de documento:
Article