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A direct requirement for Xmus101 in ATR-mediated phosphorylation of Claspin bound Chk1 during checkpoint signaling.

Yan, Shan and Lindsay, Howard D. and Michael, W. Matthew (2006) A direct requirement for Xmus101 in ATR-mediated phosphorylation of Claspin bound Chk1 during checkpoint signaling. Journal of Cell Biology, 173 (2). pp. 181-186. ISSN 0021-9525

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    Abstract

    TopBP1-like proteins, which include Xenopus laevis Xmus101, are required for DNA replication and have been linked to replication checkpoint control. A direct role for TopBP1/Mus101 in checkpoint control has been difficult to prove, however, because of the requirement for replication in generating the DNA structures that activate the checkpoint. Checkpoint activation occurs in X. laevis egg extracts upon addition of an oligonucleotide duplex (AT70). We show that AT70 bypasses the requirement for replication in checkpoint activation. We take advantage of this replication-independent checkpoint system to determine the role of Xmus101 in the checkpoint. We find that Xmus101 is essential for AT70-mediated checkpoint signaling and that it functions to promote phosphorylation of Claspin bound Chk1 by the ataxia-telangiectasia and Rad-3–related (ATR) protein kinase. We also identify a separation-of-function mutant of Xmus101. In extracts expressing this mutant, replication of sperm chromatin occurs normally; however, the checkpoint response to stalled replication forks fails. These data demonstrate that Xmus101 functions directly during signal relay from ATR to Chk1.

    Item Type: Article
    Journal or Publication Title: Journal of Cell Biology
    Subjects: Q Science > QH Natural history > QH301 Biology
    Departments: Faculty of Health and Medicine > Medicine
    ID Code: 9440
    Deposited By: Dr Howard Lindsay
    Deposited On: 10 Jun 2008 11:54
    Refereed?: Yes
    Published?: Published
    Last Modified: 26 Jul 2012 18:37
    Identification Number:
    URI: http://eprints.lancs.ac.uk/id/eprint/9440

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