Discovery - University of Dundee - Online Publications

Library & Learning Centre

Replication factory activation can be decoupled from the replication timing program by modulating Cdk levels

Replication factory activation can be decoupled from the replication timing program by modulating Cdk levels

Research output: Contribution to journalArticle

View graph of relations

Authors

  • Alexander M. Thomson
  • Peter J. Gillespie
  • J. Julian Blow (Lead / Corresponding author)

Research units

Info

Original languageEnglish
Pages209-221
Number of pages13
JournalJournal of Cell Biology
Journal publication date25 Jan 2010
Journal number2
Volume188
DOIs
StatePublished

Abstract

In the metazoan replication timing program, clusters of replication origins located in different subchromosomal domains fire at different times during S phase. We have used Xenopus laevis egg extracts to drive an accelerated replication timing program in mammalian nuclei. Although replicative stress caused checkpoint-induced slowing of the timing program, inhibition of checkpoint kinases in an unperturbed S phase did not accelerate it. Lowering cyclin-dependent kinase (Cdk) activity slowed both replication rate and progression through the timing program, whereas raising Cdk activity increased them. Surprisingly, modest alteration of Cdk activity changed the amount of DNA synthesized during different stages of the timing program. This was associated with a change in the number of active replication factories, whereas the distribution of origins within active factories remained relatively normal. The ability of Cdks to differentially effect replication initiation, factory activation, and progression through the timing program provides new insights into the way that chromosomal DNA replication is organized during S phase.

Download statistics

No data available

Documents

Documents

DOI

Library & Learning Centre

Contact | Accessibility | Policy