Discovery - University of Dundee - Online Publications

Library & Learning Centre

CDC-48/p97 Coordinates CDT-1 Degradation with GINS Chromatin Dissociation to Ensure Faithful DNA Replication

CDC-48/p97 Coordinates CDT-1 Degradation with GINS Chromatin Dissociation to Ensure Faithful DNA Replication

Research output: Contribution to journalArticle

View graph of relations

Authors

  • Andre Franz
  • Michael Orth
  • Paul A. Pirson
  • Remi Sonneville
  • J. Julian Blow
  • Anton Gartner
  • Olaf Stemmann
  • Thorsten Hoppe

Research units

Info

Original languageEnglish
Pages85-96
Number of pages12
JournalMolecular Cell
Journal publication date7 Oct 2011
Volume44
Issue1
DOIs
StatePublished
Peer-reviewedYes

Abstract

Faithful transmission of genomic information requires tight spatiotemporal regulation of DNA replication factors. In the licensing step of DNA replication, CDT-1 is loaded onto chromatin to subsequently promote the recruitment of additional replication factors, including CDC-45 and GINS. During the elongation step, the CDC-45/GINS complex moves with the replication fork; however, it is largely unknown how its chromatin association is regulated. Here, we show that the chaperone-like ATPase CDC-48/p97 coordinates degradation of CDT-1 with release of the CDC-45/GINS complex. C. elegans embryos lacking CDC-48 or its cofactors UFD-1/NPL-4 accumulate CDT-1 on mitotic chromatin, indicating a critical role of CDC-48 in CDT-1 turnover. Strikingly, CDC-48(UFD-1/NPL-4)-deficient embryos show persistent chromatin association of CDC-45/GINS, which is a consequence of CDT-1 stabilization. Moreover, our data confirmed a similar regulation in Xenopus egg extracts, emphasizing a conserved coordination of licensing and elongation events during eukaryotic DNA replication by CDC-48/p97.

Documents

Library & Learning Centre

Contact | Accessibility | Policy