Depletion of Uhrf1 inhibits chromosomal DNA replication in Xenopus egg extracts.

Depletion of Uhrf1 inhibits chromosomal DNA replication in Xenopus egg extracts.
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DOI:
10.1093/nar/gkt549
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发表时间:
2013-09
影响因子:
14.9
通讯作者:
Lindsay HD
Lindsay HD
中科院分区:
生物学2区
文献类型:
--
作者:
Taylor EM;Bonsu NM;Price RJ;Lindsay HD

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UHRF 1(泛素样,含有PHD和RING指结构域1)通过识别各种组蛋白标记和与染色质修饰蛋白相互作用在表观遗传调控中具有公认的作用。然而,其在调节细胞周期进程中的功能仍然知之甚少,并且在很大程度上归因于转录调控中的作用。在这项研究中,我们使用非洲爪蟾卵提取物来分析Uhrf1在DNA复制的转录影响的情况下的功能。我们证明,去除Uhrf1抑制在这个系统中的染色体复制。我们进一步表明,这种需要Uhrf1,或相关的因素,发生在DNA复制的早期阶段,Uhrf1耗尽的后果不仅仅是由于它的作用加载Dnmt 1到新复制的DNA。我们描述了Uhrf1染色质协会的DNA复制开始前的模式,并表明,这反映了功能的要求之前和之后的原产地许可。我们的数据表明,非洲爪蟾Uhrf1的去除影响的关键复制蛋白的染色质协会,并揭示Uhrf1作为一个重要的后生动物DNA复制所需的新因素。
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.
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