QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

Vol. 17, Issue 8, 3456-3468, August 2006

This Article Full Text Full Text (PDF) Supplemental Material All Versions of this Article: E06-01-0056v1 17/8/3456    most recent Alert me when this article is cited Alert me if a correction is posted Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Taricani, L. Articles by Wang, T. S.F. Search for Related Content PubMed PubMed Citation Articles by Taricani, L. Articles by Wang, T. S.F.

Rad4^TopBP1, a Scaffold Protein, Plays Separate Roles in DNA Damage and Replication Checkpoints and DNA Replication

Department of Pathology, Stanford University School of Medicine, Stanford, CA 94305-5324

Submitted January 23, 2006; Revised May 12, 2006; Accepted May 15, 2006
Monitoring Editor: Mark Solomon

Rad4^TopBP1, a BRCT domain protein, is required for both DNA replication and checkpoint responses. Little is known about how the multiple roles of Rad4^TopBP1 are coordinated in maintaining genome integrity. We show here that Rad4^TopBP1 of fission yeast physically interacts with the checkpoint sensor proteins, the replicative DNA polymerases, and a WD-repeat protein, Crb3. We identified four novel mutants to investigate how Rad4^TopBP1 could have multiple roles in maintaining genomic integrity. A novel mutation in the third BRCT domain of rad4^+TopBP1 abolishes DNA damage checkpoint response, but not DNA replication, replication checkpoint, and cell cycle progression. This mutant protein is able to associate with all three replicative polymerases and checkpoint proteins Rad3^ATR-Rad26^ATRIP, Hus1, Rad9, and Rad17 but has a compromised association with Crb3. Furthermore, the damaged-induced Rad9 phosphorylation is significantly reduced in this rad4^TopBP1 mutant. Genetic and biochemical analyses suggest that Crb3 has a role in the maintenance of DNA damage checkpoint and influences the Rad4^TopBP1 damage checkpoint function. Taken together, our data suggest that Rad4^TopBP1 provides a scaffold to a large complex containing checkpoint and replication proteins thereby separately enforcing checkpoint responses to DNA damage and replication perturbations during the cell cycle.

The online version of this article contains supplemental material at MBC Online (http://www.molbiolcell.org).

Address correspondence to: Teresa S.F. Wang ( tswang{at}stanford.edu)

This article has been cited by other articles:

				F. Puddu, M. Granata, L. Di Nola, A. Balestrini, G. Piergiovanni, F. Lazzaro, M. Giannattasio, P. Plevani, and M. Muzi-Falconi Phosphorylation of the Budding Yeast 9-1-1 Complex Is Required for Dpb11 Function in the Full Activation of the UV-Induced DNA Damage Checkpoint Mol. Cell. Biol., August 1, 2008; 28(15): 4782 - 4793. [Abstract] [Full Text] [PDF]

				L. Taricani and T. S. F. Wang Rad4TopBP1 Associates with Srr2, an Spc1 MAPK-regulated Protein, in Response to Environmental Stress J. Biol. Chem., March 23, 2007; 282(12): 8793 - 8800. [Abstract] [Full Text] [PDF]