DOI: 10.1101/gad.208701. The yeast Xrs2 complex functions in S phase checkpoint regulation

The yeast Xrs2 complex functions in S phase checkpoint regulation

10.1101/gad.208701

Crossref journal-article

Cold Spring Harbor Laboratory

Genes & Development (246)

Abstract

The Nbs1 complex is an evolutionarily conserved multisubunit nuclease composed of the Mre11, Rad50, and Nbs1 proteins. Hypomorphic mutations in the NBS1 or MRE11 genes in humans result in conditions characterized by DNA damage sensitivity, cell cycle checkpoint deficiency, and high cancer incidence. The equivalent complex in the yeast Saccharomyces cerevisiae (Xrs2p complex) has been implicated in DNA double-strand break repair and in telomere length regulation. Here, we find that xrs2Δ,mre11Δ, and rad50Δ mutants are markedly defective in the initiation of the intra-S phase checkpoint in response to DNA damage. Furthermore, the absence of a functional Xrs2p complex leads to sensitivity to deoxynucleotide depletion and to an inability to efficiently slow down cell cycle progression in response to hydroxyurea. The checkpoint appears to require the nuclease activity of Mre11p and its defect is associated with the abrogation of the Tel1p/Mec1p signaling pathway. Notably, DNA damage induces phosphorylation of both Xrs2p and Mre11p in a Tel1p-dependent manner. These results indicate that the Tel1p/ATM signaling pathway is conserved from yeast to humans and suggest that the Xrs2p/Nbs1 complexes act as signal modifiers.

Bibliography

DâAmours, D., & Jackson, S. P. (2001). The yeast Xrs2 complex functions in S phase checkpoint regulation. Genes & Development, 15(17), 2238â2249.

Authors 2

Damien D'Amours (first)
Stephen P. Jackson (additional)

References 45 Referenced 166

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Dates

Type	When
Created	23 years, 1 month ago (July 26, 2002, 8 p.m.)
Deposited	3 years, 9 months ago (Nov. 15, 2021, 10:43 a.m.)
Indexed	1 month, 3 weeks ago (July 2, 2025, 2:11 p.m.)
Issued	23 years, 11 months ago (Sept. 1, 2001)
Published	23 years, 11 months ago (Sept. 1, 2001)
Published Online	23 years, 11 months ago (Sept. 1, 2001)
Published Print	23 years, 11 months ago (Sept. 1, 2001)

Funders 0

None

BibTeX

@article{D_Amours_2001, title={The yeast Xrs2 complex functions in S phase checkpoint regulation}, volume={15}, ISSN={1549-5477}, url={http://dx.doi.org/10.1101/gad.208701}, DOI={10.1101/gad.208701}, number={17}, journal={Genes & Development}, publisher={Cold Spring Harbor Laboratory}, author={D’Amours, Damien and Jackson, Stephen P.}, year={2001}, month=sep, pages={2238–2249} }

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