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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
Affiliations
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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.

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References
1.
Zhu J, Newlon C, Huberman J . Localization of a DNA replication origin and termination zone on chromosome III of Saccharomyces cerevisiae. Mol Cell Biol. 1992; 12(10):4733-41. PMC: 360400. DOI: 10.1128/mcb.12.10.4733-4741.1992. View

2.
Wach A . PCR-synthesis of marker cassettes with long flanking homology regions for gene disruptions in S. cerevisiae. Yeast. 1996; 12(3):259-65. DOI: 10.1002/(SICI)1097-0061(19960315)12:3%3C259::AID-YEA901%3E3.0.CO;2-C. View

3.
Lee S, Moore J, Holmes A, Umezu K, Kolodner R, Haber J . Saccharomyces Ku70, mre11/rad50 and RPA proteins regulate adaptation to G2/M arrest after DNA damage. Cell. 1998; 94(3):399-409. DOI: 10.1016/s0092-8674(00)81482-8. View

4.
Lopes M, Pellicioli A, Liberi G, Plevani P, Muzi-Falconi M, Newlon C . The DNA replication checkpoint response stabilizes stalled replication forks. Nature. 2001; 412(6846):557-61. DOI: 10.1038/35087613. View

5.
Grenon M, Magill C, Lowndes N, Jackson S . Double-strand breaks trigger MRX- and Mec1-dependent, but Tel1-independent, checkpoint activation. FEMS Yeast Res. 2006; 6(5):836-47. DOI: 10.1111/j.1567-1364.2006.00076.x. View