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

Author

Listed:
  • 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)

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.

Suggested Citation

  • 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 &, 2016. "A replicator-specific binding protein essential for site-specific initiation of DNA replication in mammalian cells," Nature Communications, Nature, vol. 7(1), pages 1-14, September.
    • Handle: RePEc:nat:natcom:v:7:y:2016:i:1:d:10.1038_ncomms11748
    DOI: 10.1038/ncomms11748
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