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Publication : A WD-repeat protein stabilizes ORC binding to chromatin.

First Author  Shen Z Year  2010
Journal  Mol Cell Volume  40
Issue  1 Pages  99-111
PubMed ID  20932478 Mgi Jnum  J:165524
Mgi Id  MGI:4837600 Doi  10.1016/j.molcel.2010.09.021
Citation  Shen Z, et al. (2010) A WD-repeat protein stabilizes ORC binding to chromatin. Mol Cell 40(1):99-111
abstractText  Origin recognition complex (ORC) plays critical roles in the initiation of DNA replication and cell-cycle progression. In metazoans, ORC associates with origin DNA during G1 and with heterochromatin in postreplicated cells. However, what regulates the binding of ORC to chromatin is not understood. We have identified a highly conserved, leucine-rich repeats and WD40 repeat domain-containing protein 1 (LRWD1) or ORC-associated (ORCA) in human cells that interacts with ORC and modulates chromatin association of ORC. ORCA colocalizes with ORC and shows similar cell-cycle dynamics. We demonstrate that ORCA efficiently recruits ORC to chromatin. Depletion of ORCA in human primary cells and embryonic stem cells results in loss of ORC association to chromatin, concomitant reduction of MCM binding, and a subsequent accumulation in G1 phase. Our results suggest ORCA-mediated association of ORC to chromatin is critical to initiate preRC assembly in G1 and chromatin organization in post-G1 cells.
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