A Role for USP7 in DNA Replication

• DOI: 10.1128/mcb.00639-13
• Publication Date: 2013-11-05T02:33:39Z
• Authors: Madhav Jagannathan; Tin Nguyen; David Gallo; Niharika Luthra; Grant W. Brown; Vivian Saridakis; Lori Frappier
• Keywords: Minichromosome maintenance; Origin recognition complex

The minichromosome maintenance (MCM) complex, which plays multiple important roles in DNA replication, is loaded onto chromatin following mitosis, remains on until the completion of synthesis, and then unloaded by a poorly defined mechanism that involves MCM binding protein (MCM-BP). Here we show MCM-BP directly interacts with ubiquitin-specific protease USP7, this interaction occurs predominantly chromatin, can tether USP7 to proteins. Detailed biochemical structure analyses USP7-MCM-BP showed (155)PSTS(158) sequence mediates critical interactions TRAF domain pocket USP7. Analysis effects knockout replication revealed lack results slowed progression through late S phase without globally affecting fork rate or origin usage. Lack also resulted increased levels proteins investigation cause increase defect dissociation from mid- phase. This role mirrors previously described for complex unloading suggests works unload complexes at end