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Analysis of Rad3 and Chk1 protein kinases defines different checkpoint responses.

Martinho, Rui G. and Lindsay, Howard D. and Flaggs, Gail and DeMaggio, Anthony J and Hoekstra, Merl F. and Carr, Antony M. and Bentley, Nicola J. (1998) Analysis of Rad3 and Chk1 protein kinases defines different checkpoint responses. EMBO Journal, 17 (24). pp. 7239-7249. ISSN 0261-4189

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    Abstract

    Eukaryotic cells respond to DNA damage and S phase replication blocks by arresting cell-cycle progression through the DNA structure checkpoint pathways. In Schizosaccharomyces pombe, the Chk1 kinase is essential for mitotic arrest and is phosphorylated after DNA damage. During S phase, the Cds1 kinase is activated in response to DNA damage and DNA replication blocks. The response of both Chk1 and Cds1 requires the six 'checkpoint Rad' proteins (Rad1, Rad3, Rad9, Rad17, Rad26 and Hus1). We demonstrate that DNA damage-dependent phosphorylation of Chk1 is also cell-cycle specific, occurring primarily in late S phase and G2, but not during M/G1 or early S phase. We have also isolated and characterized a temperature-sensitive allele of rad3. Rad3 functions differently depending on which checkpoint pathway is activated. Following DNA damage, rad3 is required to initiate but not maintain the Chk1 response. When DNA replication is inhibited, rad3 is required for both initiation and maintenance of the Cds1 response. We have identified a strong genetic interaction between rad3 and cds1, and biochemical evidence shows a physical interaction is possible between Rad3 and Cds1, and between Rad3 and Chk1 in vitro. Together, our results highlight the cell-cycle specificity of the DNA structure-dependent checkpoint response and identify distinct roles for Rad3 in the different checkpoint responses.

    Item Type: Article
    Journal or Publication Title: EMBO Journal
    Uncontrolled Keywords: ATM ; ATR ; cell-cycle checkpoints ; Chk1 ; Rad3
    Subjects: Q Science > QH Natural history > QH301 Biology
    Departments: Faculty of Health and Medicine > Medicine
    ID Code: 28092
    Deposited By: Dr Howard Lindsay
    Deposited On: 09 Nov 2009 10:00
    Refereed?: Yes
    Published?: Published
    Last Modified: 26 Jul 2012 16:44
    Identification Number:
    URI: http://eprints.lancs.ac.uk/id/eprint/28092

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