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 Bioljournal_title
Molecular and cellular biologyauthors
Alvino GM,Collingwood D,Murphy JM,Delrow J,Brewer BJ,Raghuraman MKdoi
10.1128/MCB.00719-07subject
Has Abstractpub_date
2007-09-01 00:00:00pages
6396-406issue
18eissn
0270-7306issn
1098-5549pii
MCB.00719-07journal_volume
27pub_type
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