Format

Send to

Choose Destination
Nat Commun. 2016 Jun 8;7:11748. doi: 10.1038/ncomms11748.

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

Author information

1
Developmental Therapeutics Branch, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, Maryland 20892, USA.
2
In Silico Solutions, Fairfax, Virginia 22033, USA.
3
Department of Animal Science, Cornell University, Ithaca, New York 14853-4801, USA.

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.

PMID:
27272143
PMCID:
PMC4899857
DOI:
10.1038/ncomms11748
[Indexed for MEDLINE]
Free PMC Article

Supplemental Content

Full text links

Icon for Nature Publishing Group Icon for PubMed Central
Loading ...
Support Center