A Replicator-Specific Binding Protein Essential for Site-Specific Initiation of DNA Replication in Mammalian Cells

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

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.

Publication types

  • Research Support, N.I.H., Intramural

MeSH terms

  • Animals
  • Base Sequence
  • Cell Line
  • DNA Replication*
  • DNA-Binding Proteins / metabolism*
  • Embryo, Mammalian / cytology
  • Fibroblasts / metabolism
  • Genetic Loci
  • Genome
  • Humans
  • Locus Control Region
  • Mammals / metabolism*
  • Mice
  • Models, Biological
  • Protein Binding
  • Replication Origin*

Substances

  • DNA-Binding Proteins