Replication in hydroxyurea: it's a matter of time.

Abstract:

:Hydroxyurea (HU) is a DNA replication inhibitor that negatively affects both the elongation and initiation phases of replication and triggers the "intra-S phase checkpoint." Previous work with budding yeast has shown that, during a short exposure to HU, MEC1/RAD53 prevent initiation at some late S phase origins. In this study, we have performed microarray experiments to follow the fate of all origins over an extended exposure to HU. We show that the genome-wide progression of DNA synthesis, including origin activation, follows the same pattern in the presence of HU as in its absence, although the time frames are very different. We find no evidence for a specific effect that excludes initiation from late origins. Rather, HU causes S phase to proceed in slow motion; all temporal classes of origins are affected, but the order in which they become active is maintained. We propose a revised model for the checkpoint response to HU that accounts for the continued but slowed pace of the temporal program of origin activation.

journal_name

Mol Cell Biol

authors

Alvino GM,Collingwood D,Murphy JM,Delrow J,Brewer BJ,Raghuraman MK

doi

10.1128/MCB.00719-07

subject

Has Abstract

pub_date

2007-09-01 00:00:00

pages

6396-406

issue

18

eissn

0270-7306

issn

1098-5549

pii

MCB.00719-07

journal_volume

27

pub_type

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