In:
Journal of Cell Biology, Rockefeller University Press, Vol. 201, No. 3 ( 2013-04-29), p. 373-383
Abstract:
DNA damage slows DNA synthesis at replication forks; however, the mechanisms remain unclear. Cdc7 kinase is required for replication origin activation, is a target of the intra-S checkpoint, and is implicated in the response to replication fork stress. Remarkably, we found that replication forks proceed more rapidly in cells lacking Cdc7 function than in wild-type cells. We traced this effect to reduced origin firing, which results in fewer replication forks and a consequent decrease in Rad53 checkpoint signaling. Depletion of Orc1, which acts in origin firing differently than Cdc7, had similar effects as Cdc7 depletion, consistent with decreased origin firing being the source of these defects. In contrast, mec1-100 cells, which initiate excess origins and also are deficient in checkpoint activation, showed slower fork progression, suggesting the number of active forks influences their rate, perhaps as a result of competition for limiting factors.
Type of Medium:
Online Resource
ISSN:
1540-8140
,
0021-9525
DOI:
10.1083/jcb.201208060
Language:
English
Publisher:
Rockefeller University Press
Publication Date:
2013
detail.hit.zdb_id:
1421310-2
SSG:
12
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