Mre11 complex and DNA replication: linkage to E2F and sites of DNA synthesis.
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.
Maser
R S
RS
Laboratory of Genetics, University of Wisconsin Medical School, 445 Henry Mall, Madison, WI 53706, USA.
Mirzoeva
O K
OK
Wells
J
J
Olivares
H
H
Williams
B R
BR
Zinkel
R A
RA
Farnham
P J
PJ
Petrini
J H
JH
D000818:Animals; D001665:Binding Sites; D018797:Cell Cycle Proteins; D002460:Cell Line; D045643:DNA Repair Enzymes; D004261:DNA Replication; D004268:DNA-Binding Proteins / Q000378:metabolism*; D050684:E2F Transcription Factors; D006367:HeLa Cells; D006801:Humans; D000076228:MRE11 Homologue Protein; D051379:Mice; D009687:Nuclear Proteins / Q000378:metabolism; D010766:Phosphorylation; D016196:S Phase; D015398:Signal Transduction; D014157:Transcription Factors / Q000378:metabolism*; D014407:Tumor Cells, Cultured
D018797:Cell Cycle Proteins; D004268:DNA-Binding Proteins; D050684:E2F Transcription Factors; C121766:MRE11 protein, human; C512689:Mre11a protein, mouse; D009687:Nuclear Proteins; D014157:Transcription Factors; D000076228:MRE11 Homologue Protein; D045643:DNA Repair Enzymes