Depletion of Uhrf1 inhibits chromosomal DNA replication in Xenopus egg extracts

Taylor, Elaine and Bonsu-Dartnall, Nicola and Price, Jordan and Lindsay, Howard (2013) Depletion of Uhrf1 inhibits chromosomal DNA replication in Xenopus egg extracts. Nucleic Acids Research, 41 (16). pp. 7725-7737. ISSN 0305-1048

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Abstract

UHRF1 (ubiquitin-like, containing PHD and RING finger domains 1) has a well-established role in epigenetic regulation through the recognition of various histone marks and interaction with chromatin-modifying proteins. However, its function in regulating cell cycle progression remains poorly understood and has been largely attributed to a role in transcriptional regulation. In this study we have used Xenopus laevis egg extracts to analyse Uhrf1 function in DNA replication in the absence of transcriptional influences. We demonstrate that removal of Uhrf1 inhibits chromosomal replication in this system. We further show that this requirement for Uhrf1, or an associated factor, occurs at an early stage of DNA replication and that the consequences of Uhrf1 depletion are not solely due to its role in loading Dnmt1 onto newly replicated DNA. We describe the pattern of Uhrf1 chromatin association before the initiation of DNA replication and show that this reflects functional requirements both before and after origin licensing. Our data demonstrate that the removal of Xenopus Uhrf1 influences the chromatin association of key replication proteins and reveal Uhrf1 as an important new factor required for metazoan DNA replication.

Item Type:
Journal Article
Journal or Publication Title:
Nucleic Acids Research
Additional Information:
© The Author(s) 2013. Published by Oxford University Press. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/3.0/), which permits unrestricted reuse, distribution, and reproduction in any medium, provided the original work is properly cited.
Uncontrolled Keywords:
/dk/atira/pure/subjectarea/asjc/1300/1311
Subjects:
?? genetics ??
ID Code:
65525
Deposited By:
Deposited On:
08 Jul 2013 11:55
Refereed?:
Yes
Published?:
Published
Last Modified:
18 Mar 2024 00:26