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Molecular and Cellular Biology, September 2001, p. 6006-6016, Vol. 21, No. 17
0270-7306/01/$04.00+0   DOI: 10.1128/MCB.21.17.6006-6016.2001
Copyright © 2001, American Society for Microbiology. All rights reserved.

Mre11 Complex and DNA Replication: Linkage to E2F and Sites of DNA Synthesis†

Richard S. Maser,1 Olga K. Mirzoeva,1 Julie Wells,2 Heidi Olivares,1 Bret R. Williams,3 Robert A. Zinkel,1 Peggy J. Farnham,2 and John H. J. Petrini1,3,*

Laboratory of Genetics,1 McArdle Laboratory for Cancer Research,2 and Program in Cell and Molecular Biology,3 University of Wisconsin Medical School, Madison, Wisconsin 53706

Received 27 March 2001/Returned for modification 6 May 2001/Accepted 22 May 2001

We show that the Mre11 complex associates with E2F family members via the Nbs1 N terminus. This association and Nbs1 phosphorylation are correlated with S-phase checkpoint proficiency, whereas neither is sufficient individually for checkpoint activation. The Nbs1 E2F interaction occurred near the Epstein-Barr virus origin of replication as well as near a chromosomal replication origin in the c-myc promoter region and was restricted to S-phase cells. The Mre11 complex colocalized with PCNA at replication forks throughout S phase, both prior to and coincident with the appearance of nascent DNA. These data suggest that the Mre11 complex suppresses genomic instability through its influence on both the regulation and progression of DNA replication.

* Corresponding author. Mailing address: University of Wisconsin---Madison, Laboratory of Genetics, 445 Henry Mall, Madison, WI 53706. Phone: (608) 265-6043. Fax: (608) 262-2976. E-mail: jpetrini{at}facstaff.wisc.edu.

dagger Report 3572 from the University of Wisconsin---Madison Laboratory of Genetics.

Molecular and Cellular Biology, September 2001, p. 6006-6016, Vol. 21, No. 17
0270-7306/01/$04.00+0   DOI: 10.1128/MCB.21.17.6006-6016.2001
Copyright © 2001, American Society for Microbiology. All rights reserved.


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