A replicator-specific binding protein essential for site-specific initiation of DNA replication in mammalian cells

Ya Zhang, Liang Huang, Haiqing Fu, Owen K. Smith, Chii Mei Lin, Koichi Utani, Mishal Rao, William C. Reinhold, Christophe E. Redon, Michael Ryan, RyangGuk Kim, Yang You, Harlington Hanna, Yves Boisclair, Qiaoming Long and Mirit I. Aladjem ()
Additional contact information
Ya Zhang: Developmental Therapeutics Branch, Center for Cancer Research, National Cancer Institute, National Institutes of Health
Liang Huang: Developmental Therapeutics Branch, Center for Cancer Research, National Cancer Institute, National Institutes of Health
Haiqing Fu: Developmental Therapeutics Branch, Center for Cancer Research, National Cancer Institute, National Institutes of Health
Owen K. Smith: Developmental Therapeutics Branch, Center for Cancer Research, National Cancer Institute, National Institutes of Health
Chii Mei Lin: Developmental Therapeutics Branch, Center for Cancer Research, National Cancer Institute, National Institutes of Health
Koichi Utani: Developmental Therapeutics Branch, Center for Cancer Research, National Cancer Institute, National Institutes of Health
Mishal Rao: Developmental Therapeutics Branch, Center for Cancer Research, National Cancer Institute, National Institutes of Health
William C. Reinhold: Developmental Therapeutics Branch, Center for Cancer Research, National Cancer Institute, National Institutes of Health
Christophe E. Redon: Developmental Therapeutics Branch, Center for Cancer Research, National Cancer Institute, National Institutes of Health
Michael Ryan: In Silico Solutions
RyangGuk Kim: In Silico Solutions
Yang You: Developmental Therapeutics Branch, Center for Cancer Research, National Cancer Institute, National Institutes of Health
Harlington Hanna: Developmental Therapeutics Branch, Center for Cancer Research, National Cancer Institute, National Institutes of Health
Yves Boisclair: Cornell University
Qiaoming Long: Cornell University
Mirit I. Aladjem: Developmental Therapeutics Branch, Center for Cancer Research, National Cancer Institute, National Institutes of Health

Nature Communications, 2016, vol. 7, issue 1, 1-14

Abstract: Abstract Mammalian chromosome replication starts from distinct sites; however, the principles governing initiation site selection are unclear because proteins essential for DNA replication do not exhibit sequence-specific DNA binding. Here we identify a replication-initiation determinant (RepID) protein that binds a subset of replication-initiation sites. A large fraction of RepID-binding sites share a common G-rich motif and exhibit elevated replication initiation. RepID is required for initiation of DNA replication from RepID-bound replication origins, including the origin at the human beta-globin (HBB) locus. At HBB, RepID is involved in an interaction between the replication origin (Rep-P) and the locus control region. RepID-depleted murine embryonic fibroblasts exhibit abnormal replication fork progression and fewer replication-initiation events. These observations are consistent with a model, suggesting that RepID facilitates replication initiation at a distinct group of human replication origins.

Date: 2016
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DOI: 10.1038/ncomms11748

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