A WD-repeat protein stabilizes ORC binding to chromatin

Zhen Shen, Kizhakke M. Sathyan, Yijie Geng, Ruiping Zheng, Arindam Chakraborty, Brian Freeman, Fei Wang, Kannanganattu V. Prasanth, Supriya G. Prasanth

Research output: Contribution to journalArticle

Abstract

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.

Original languageEnglish (US)
Pages (from-to)99-111
Number of pages13
JournalMolecular cell
Volume40
Issue number1
DOIs
StatePublished - Oct 8 2010

ASJC Scopus subject areas

  • Molecular Biology
  • Cell Biology

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