TY - JOUR
T1 - A WD-repeat protein stabilizes ORC binding to chromatin
AU - Shen, Zhen
AU - Sathyan, Kizhakke M.
AU - Geng, Yijie
AU - Zheng, Ruiping
AU - Chakraborty, Arindam
AU - Freeman, Brian
AU - Wang, Fei
AU - Prasanth, Kannanganattu V.
AU - Prasanth, Supriya G.
N1 - Funding Information:
We thank members of the Prasanth laboratory for discussions and suggestions. We thank X. Cao, J. Chen, J. Cook, M. Dundr, A. Dutta, Y. Ge, P. Leiberman, M. Li, C. Mizzen, T. Nakamura, B. Pilas, D. Spector, B. Stillman, and P. Yao for providing reagents and suggestions. We would like to thank P. Newmark and D. Rivier for critical reading of the paper. This work was supported by a special fellowship from Leukemia and Lymphoma Society, startup funds, University of Illinois at Urbana-Champaign (UIUC), and a National Science Foundation award (0843604) to S.G.P. and by start-up funds, UIUC to K.V.P.
PY - 2010/10/8
Y1 - 2010/10/8
N2 - 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.
AB - 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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U2 - 10.1016/j.molcel.2010.09.021
DO - 10.1016/j.molcel.2010.09.021
M3 - Article
C2 - 20932478
AN - SCOPUS:77957345690
SN - 1097-2765
VL - 40
SP - 99
EP - 111
JO - Molecular cell
JF - Molecular cell
IS - 1
ER -