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PMID: 17130285 Published · ppublish English Journal Article Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov't

An FHA domain-mediated protein interaction network of Rad53 reveals its role in polarized cell growth.

The Journal of cell biology ·Vol. 175 ·No. 5 ·2006-12-04 ·Pages 743-53

Smolka MB, Chen SH, Maddox PS, Enserink JM, Albuquerque CP, Wei XX, Desai A, Kolodner RD, Zhou H

Abstract

The DNA damage checkpoint kinase Rad53 is important for the survival of budding yeast under genotoxic stresses. We performed a biochemical screen to identify proteins with specific affinity for the two Forkhead associated (FHA) domains of Rad53. The N-terminal FHA1 domain was found to coordinate a complex protein interaction network, which includes nuclear proteins involved in DNA damage checkpoints and transcriptional regulation. Unexpectedly, cytosolic proteins involved in cytokinesis, including septins, were also found as FHA1 binding proteins. Consistent with this interaction, a Rad53 mutant defective in its nuclear localization was found to localize to the bud neck. Abnormal morphology was observed in cells overexpressing the FHA1 domain and in rad53Delta cells under DNA replication stress. Further, septin Shs1 appears to have an important role in the response to DNA replication stress. Collectively, the results suggest a novel function of Rad53 in the regulation of polarized cell growth in response to DNA replication stress.

MeSH Terms
Carrier Proteins/metabolism Cell Cycle Proteins/genetics,metabolism,physiology Cell Enlargement Cell Polarity Checkpoint Kinase 2 DNA Replication Forkhead Transcription Factors/genetics Models, Biological Protein Serine-Threonine Kinases/genetics,metabolism,physiology Protein Structure, Tertiary Proteomics/methods Saccharomyces cerevisiae/growth & development,metabolism,ultrastructure Saccharomyces cerevisiae Proteins/genetics,metabolism,physiology Signal Transduction
Chemicals
Carrier Proteins Cell Cycle Proteins Forkhead Transcription Factors SHS1 protein, S cerevisiae Saccharomyces cerevisiae Proteins Checkpoint Kinase 2 Protein Serine-Threonine Kinases RAD53 protein, S cerevisiae
Authors & Affiliations
9 authors, click to expand affiliations / ORCID
Smolka Marcus B
Ludwig Institute for Cancer Research, Department of Cellular and Molecular Medicine, University of California, San Diego, La Jolla, CA 92093, USA.
Chen Sheng-hong
Maddox Paul S
Enserink Jorrit M
Albuquerque Claudio P
Wei Xiao X
Desai Arshad
Kolodner Richard D
Zhou Huilin
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Article Info
Journal
The Journal of cell biology
Abbr.
J Cell Biol
ISSN
0021-9525
DOI
10.1083/jcb.200605081
Published
2006-12-04
Epub
2006-00-27
Pages
743-53
Language
English
Region
United States
NLM ID
0375356
PMCID
PMC2064674
Subset
IM
Grants
NIGMS NIH HHS · GM26017 · United States
NIGMS NIH HHS · R37 GM026017 · United States
NHGRI NIH HHS · HG002604 · United States
NHGRI NIH HHS · K22 HG002604 · United States
NHGRI NIH HHS · K22 HG002604-04 · United States
NIGMS NIH HHS · R01 GM026017 · United States
External Links
PubMed source DOI: 10.1083/jcb.200605081 PMC Full Text View journal details
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