A replicator-specific binding protein essential for site-specific initiation of DNA replication in mammalian cells.
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.
Developmental Therapeutics Branch, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, Maryland 20892, USA.
Ya
Y
Zhang
Developmental Therapeutics Branch, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, Maryland 20892, USA.
Liang
0000-0003-1663-7025
L
Huang
Developmental Therapeutics Branch, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, Maryland 20892, USA.
Haiqing
H
Fu
Developmental Therapeutics Branch, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, Maryland 20892, USA.
Owen K
OK
Smith
Developmental Therapeutics Branch, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, Maryland 20892, USA.
Chii Mei
CM
Lin
Developmental Therapeutics Branch, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, Maryland 20892, USA.
Koichi
K
Utani
Developmental Therapeutics Branch, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, Maryland 20892, USA.
Mishal
M
Rao
Developmental Therapeutics Branch, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, Maryland 20892, USA.
William C
WC
Reinhold
Developmental Therapeutics Branch, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, Maryland 20892, USA.
Christophe E
CE
Redon
In Silico Solutions, Fairfax, Virginia 22033, USA.
Michael
M
Ryan
In Silico Solutions, Fairfax, Virginia 22033, USA.
RyangGuk
R
Kim
Developmental Therapeutics Branch, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, Maryland 20892, USA.
Yang
Y
You
Developmental Therapeutics Branch, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, Maryland 20892, USA.
Harlington
H
Hanna
Department of Animal Science, Cornell University, Ithaca, New York 14853-4801, USA.
Yves
Y
Boisclair
Department of Animal Science, Cornell University, Ithaca, New York 14853-4801, USA.
Qiaoming
Q
Long
Developmental Therapeutics Branch, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, Maryland 20892, USA.
Mirit I
MI
Aladjem
D000818:Animals; D001483:Base Sequence; D002460:Cell Line; D004261:DNA Replication; D004268:DNA-Binding Proteins / Q000378:metabolism*; D004622:Embryo, Mammalian / Q000166:cytology; D005347:Fibroblasts / Q000378:metabolism; D056426:Genetic Loci; D016678:Genome; D006801:Humans; D019901:Locus Control Region; D008322:Mammals / Q000378:metabolism*; D051379:Mice; D008954:Models, Biological; D011485:Protein Binding; D018741:Replication Origin
D004268:DNA-Binding Proteins