In:
eLife, eLife Sciences Publications, Ltd, Vol. 6 ( 2017-11-06)
Kurzfassung:
The cellular pathways that restart stalled replication forks are essential for genome stability and tumor prevention. However, how many of these pathways exist in cells and how these pathways are selectively activated remain unclear. Here, we describe two major fork restart pathways, and demonstrate that their selection is governed by 53BP1 and BRCA1, which are known to control the pathway choice to repair double-strand DNA breaks (DSBs). Specifically, 53BP1 promotes a fork cleavage-free pathway, whereas BRCA1 facilitates a break-induced replication (BIR) pathway coupled with SLX-MUS complex-mediated fork cleavage. The defect in the first pathway, but not DSB repair, in a 53BP1 mutant is largely corrected by disrupting BRCA1, and vice versa. Moreover, PLK1 temporally regulates the switch of these two pathways through enhancing the assembly of the SLX-MUS complex. Our results reveal two distinct fork restart pathways, which are antagonistically controlled by 53BP1 and BRCA1 in a DSB repair-independent manner.
Materialart:
Online-Ressource
ISSN:
2050-084X
DOI:
10.7554/eLife.30523.001
DOI:
10.7554/eLife.30523.002
DOI:
10.7554/eLife.30523.003
DOI:
10.7554/eLife.30523.004
DOI:
10.7554/eLife.30523.005
DOI:
10.7554/eLife.30523.006
DOI:
10.7554/eLife.30523.007
DOI:
10.7554/eLife.30523.008
DOI:
10.7554/eLife.30523.009
DOI:
10.7554/eLife.30523.010
DOI:
10.7554/eLife.30523.011
DOI:
10.7554/eLife.30523.012
DOI:
10.7554/eLife.30523.013
DOI:
10.7554/eLife.30523.014
DOI:
10.7554/eLife.30523.015
DOI:
10.7554/eLife.30523.016
DOI:
10.7554/eLife.30523.019
DOI:
10.7554/eLife.30523.020
DOI:
10.7554/eLife.30523.018
Sprache:
Englisch
Verlag:
eLife Sciences Publications, Ltd
Publikationsdatum:
2017
ZDB Id:
2687154-3