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Delineating the position of rad4+/cut5+ within the DNA-structure checkpoint pathways in Schizosaccharomyces pombe.

Harris, Sheila and Kemplen, Caroline and Caspari, Thomas and Chan, Christopher and Lindsay, Howard D. and Poitelea, Marius and Carr, Antony M. and Price, Clive (2003) Delineating the position of rad4+/cut5+ within the DNA-structure checkpoint pathways in Schizosaccharomyces pombe. Journal of Cell Science, 116 (17). pp. 3519-3529. ISSN 0021-9533

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Abstract

The fission yeast BRCT domain protein Rad4/Cut5 is required for genome integrity checkpoint responses and DNA replication. Here we address the position at which Rad4/Cut5 acts within the checkpoint response pathways. Rad4 is shown to act upstream of the effector kinases Chk1 and Cds1, as both Chk1 phosphorylation and Cds1 kinase activity require functional Rad4. Phosphorylation of Rad9, Rad26 and Hus1 in response to either DNA damage or inhibition of DNA replication are independent of Rad4/Cut5 checkpoint function. Further we show that a novel, epitope-tagged allele of rad4+/cut5+ acts as a dominant suppressor of the checkpoint deficiencies of rad3-, rad26- and rad17- mutants. Suppression results in the restoration of mitotic arrest and is dependent upon the remaining checkpoint Rad proteins and the two effector kinases. High-level expression of the rad4+/cut5+ allele in rad17 mutant cells restores the nuclear localization of Rad9, but this does not fully account for the observed suppression. We conclude from these data that Rad4/Cut5 acts with Rad3, Rad26 and Rad17 to effect the checkpoint response, and a model for its function is discussed.

Item Type: Article
Journal or Publication Title: Journal of Cell Science
Uncontrolled Keywords: Rad4 ; Chk1 ; Checkpoint control ; Genome integrity ; DNA damage ; DNA replication
Subjects: Q Science > QH Natural history > QH301 Biology
Departments: Faculty of Health and Medicine > Medicine
Faculty of Health and Medicine > Biomedical & Life Sciences
ID Code: 9313
Deposited By: Dr Clive Price
Deposited On: 04 Jun 2008 12:02
Refereed?: Yes
Published?: Published
Last Modified: 26 Jul 2012 18:35
Identification Number:
URI: http://eprints.lancs.ac.uk/id/eprint/9313

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