DNA replication initiates at different sites in early and late S phase within human ribosomal RNA genes

Frederick D. Coffman, Mai He, Mai Ling Diaz, Stanley Cohen

Research output: Contribution to journalArticlepeer-review

14 Scopus citations

Abstract

Metazoan replication origins often contain multiple potential initiation sites, and the selection of which of the potential sites are used appears to be dependent upon multiple factors, including the state of differentiation, cell metabolism, and local transcriptional activity. Numerous studies have shown that a replication origin exists within the non-transcribed spacer region of the human ribosomal RNA gene. We here analyze nascent leading strand DNA from S phase human lymphoid cells, and find that while the majority of rDNA replicates in mid- and late S phase and preferentially initiates replication 6 kbp from the transcription start site, in very early S phase the preferred initiation site is much closer to the transcription start site and may involve rDNA promoter sequences. This early site is coincident with a minimum GC skew value, diagnostic for replication origins in bacteria and yeast. These results suggest that replication timing can influence initiation site selection. The timing and nucleolar localization of rDNA further suggest that this site likely participates in the small number of perinucleolar initiation foci observed in very early S phase cells that represent the beginning of cellular DNA replication.

Original languageEnglish
Pages (from-to)1223-1226
Number of pages4
JournalCell Cycle
Volume4
Issue number9
DOIs
StatePublished - Sep 2005

Keywords

  • Cell cycle
  • Initiation site
  • Promoter region
  • Replication initiation
  • Replication origin
  • rDNA

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