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53BP1 and the LINC Complex Promote Microtubule-Dependent DSB Mobility and DNA Repair.
- Source :
-
Cell [Cell] 2015 Nov 05; Vol. 163 (4), pp. 880-93. - Publication Year :
- 2015
-
Abstract
- 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.<br /> (Copyright © 2015 Elsevier Inc. All rights reserved.)
- Subjects :
- Animals
Carrier Proteins metabolism
DNA End-Joining Repair
Humans
Intracellular Signaling Peptides and Proteins metabolism
Membrane Proteins genetics
Membrane Proteins metabolism
Mice
Mice, Knockout
Microtubule-Associated Proteins genetics
Microtubule-Associated Proteins metabolism
Nuclear Proteins metabolism
Phosphorylation
Telomere
Telomere-Binding Proteins genetics
Telomere-Binding Proteins metabolism
Telomeric Repeat Binding Protein 2 metabolism
Tumor Suppressor p53-Binding Protein 1
Chromosomal Proteins, Non-Histone metabolism
DNA Breaks, Double-Stranded
DNA Repair
DNA-Binding Proteins metabolism
Microtubules metabolism
Subjects
Details
- Language :
- English
- ISSN :
- 1097-4172
- Volume :
- 163
- Issue :
- 4
- Database :
- MEDLINE
- Journal :
- Cell
- Publication Type :
- Academic Journal
- Accession number :
- 26544937
- Full Text :
- https://doi.org/10.1016/j.cell.2015.09.057