Persistent initiation of DNA replication and chromatin-bound MCM proteins during the cell cycle in cdc6 mutants.

Abstract:

:Faithful inheritance of genetic information requires that DNA be copied only once each cell cycle. Initiation of DNA replication involves the establishment of a prereplication complex (pre-RC) and subsequent activation by CDK/cyclins, converting the pre-RC to a post-RC. The origin recognition complex (ORC), Cdc6p, and the MCM proteins are required for establishing the pre-RC. We show that all six ORC subunits remain bound to chromatin throughout the cell cycle, whereas the MCM proteins cycle on and off, corresponding precisely to transitions of the RC. A newly isolated cdc6 mutant displays promiscuous initiation of DNA replication, increased nuclear DNA content, and constant MCM protein association with chromatin throughout the cell cycle. This gain-of-function cdc6 mutant ignores the negative controls imposed normally on initiation by the CDK/cyclins, suggesting that Cdc6p is a key mediator of once-per-cell-cycle control of DNA replication.

journal_name

Genes Dev

journal_title

Genes & development

authors

Liang C,Stillman B

doi

10.1101/gad.11.24.3375

subject

Has Abstract

pub_date

1997-12-15 00:00:00

pages

3375-86

issue

24

eissn

0890-9369

issn

1549-5477

journal_volume

11

pub_type

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