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Nucleic Acids Res 2013 Sep 01;4116:7725-37. doi: 10.1093/nar/gkt549.
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Depletion of Uhrf1 inhibits chromosomal DNA replication in Xenopus egg extracts.

Taylor EM , Bonsu NM , Price RJ , Lindsay HD .

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.

PubMed ID: 23788677
PMC ID: PMC3763540
Article link: Nucleic Acids Res
Grant support: [+]

Species referenced: Xenopus laevis
Genes referenced: cdc45 dnmt1 gmnn h2ac21 orc1 orc2 uhrf1
Antibodies: Cdc45 Ab1 Dnmt1 Ab1 H2afj Ab1 H3f3a Ab7 Mcm7 Ab1 Orc1 Ab1 Orc2 Ab1 Pcna Ab2 Uhrf1 Ab1 Uhrf1 Ab2

Article Images: [+] show captions
References [+] :
Achour, UHRF1 recruits the histone acetyltransferase Tip60 and controls its expression and activity. 2009, Pubmed