Maser R S, Mirzoeva O K, Wells J, Olivares H, Williams B R, Zinkel R A, Farnham P J, Petrini J H
Laboratory of Genetics, University of Wisconsin Medical School, 445 Henry Mall, Madison, WI 53706, USA.
Mol Cell Biol. 2001 Sep;21(17):6006-16. doi: 10.1128/MCB.21.17.6006-6016.2001.
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.
我们发现Mre11复合物通过Nbs1的N端与E2F家族成员相互作用。这种相互作用以及Nbs1的磷酸化与S期检查点功能相关,然而单独任何一个都不足以激活检查点。Nbs1与E2F的相互作用发生在爱泼斯坦-巴尔病毒复制起点附近以及c-myc启动子区域的一个染色体复制起点附近,并且仅限于S期细胞。在整个S期,Mre11复合物在复制叉处与增殖细胞核抗原(PCNA)共定位,无论是在新生DNA出现之前还是同时。这些数据表明,Mre11复合物通过影响DNA复制的调控和进程来抑制基因组不稳定。