Replicon Dynamics, Dormant Origin Firing, and Terminal Fork Integrity After Double-strand Break Formation

Overview

Journal Cell

Publisher Cell Press

Specialty Cell Biology

Date 2009 Apr 14

PMID 19361851

Citations 70

Authors

Ylli Doksani

Rodrigo Bermejo

Simona Fiorani

James E Haber

Marco Foiani

Affiliations

Soon will be listed here.

Abstract

In response to replication stress, the Mec1/ATR and SUMO pathways control stalled- and damaged-fork stability. We investigated the S phase response at forks encountering a broken template (termed the terminal fork). We show that double-strand break (DSB) formation can locally trigger dormant origin firing. Irreversible fork resolution at the break does not impede progression of the other fork in the same replicon (termed the sister fork). The Mre11-Tel1/ATM response acts at terminal forks, preventing accumulation of cruciform DNA intermediates that tether sister chromatids and can undergo nucleolytic processing. We conclude that sister forks can be uncoupled during replication and that, after DSB-induced fork termination, replication is rescued by dormant origin firing or adjacent replicons. We have uncovered a Tel1/ATM- and Mre11-dependent response controlling terminal fork integrity. Our findings have implications for those genome instability syndromes that accumulate DNA breaks during S phase and for forks encountering eroding telomeres.

Citing Articles

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