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Science 297 (5581): 602-606

Copyright © 2002 by the American Association for the Advancement of Science

ATR Homolog Mec1 Promotes Fork Progression, Thus Averting Breaks in Replication Slow Zones

Rita S. Cha, Nancy Kleckner*

Budding yeast Mec1, homolog of mammalian ATR, is an essential protein that mediates S-phase checkpoint responses and meiotic recombination. Elimination of Mec1 function leads to genomewide fork stalling followed by chromosome breakage. Breaks do not result from stochastic collapse of stalled forks or other incidental lesions; instead, they occur in specific regions of the genome during a G2 chromosomal transition. Break regions are found to be genetically encoded replication slow zones (RSZs), a newly discovered yeast chromosomal determinant. Thus, Mec1 has important functions in normal S phase and the genome instability of mec1 (and, analogously, ATR-/-) mutants stems from defects in these basic roles.

Department of Molecular and Cellular Biology, Harvard University, Cambridge, MA 02138, USA.
*   To whom correspondence should be addressed. E-mail: kleckner{at}fas.harvard.edu.

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