Human DNA polymerase epsilon colocalizes with proliferating cell nuclear antigen and DNA replication late, but not early, in S phase

J Biol Chem. 2002 Mar 8;277(10):8658-66. doi: 10.1074/jbc.M110615200. Epub 2001 Dec 10.

Abstract

DNA polymerase epsilon (pol epsilon) has been implicated in DNA replication, DNA repair, and cell cycle control, but its precise roles are unclear. When the subcellular localization of human pol epsilon was examined by indirect immunofluorescence, pol epsilon appeared in discrete nuclear foci that colocalized with proliferating cell nuclear antigen (PCNA) foci and sites of DNA synthesis only late in S phase. Early in S phase, pol epsilon foci were adjacent to PCNA foci. In contrast to PCNA foci that were only present in S phase, pol epsilon foci were present throughout mitosis and the G(1) phase of cycling cells. It is hypothesized from these observations that pol epsilon and PCNA have separate but associated functions early in S phase and that pol epsilon participates with PCNA in DNA replication late in S phase.

Publication types

  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Antimetabolites / pharmacology
  • Antineoplastic Agents / pharmacology
  • Bromodeoxyuridine / pharmacology
  • Cell Division
  • Cell Nucleus / metabolism
  • Cells, Cultured
  • DNA / biosynthesis*
  • DNA Damage
  • DNA Polymerase II / chemistry*
  • DNA Polymerase II / metabolism*
  • DNA Repair
  • Fibroblasts / metabolism
  • Flow Cytometry
  • Humans
  • Microscopy, Confocal
  • Microscopy, Fluorescence
  • Mitosis
  • Models, Biological
  • Nocodazole / pharmacology
  • Proliferating Cell Nuclear Antigen / chemistry
  • Proliferating Cell Nuclear Antigen / metabolism*
  • Protein Binding
  • Radiation-Sensitizing Agents / pharmacology
  • S Phase*
  • Ultraviolet Rays

Substances

  • Antimetabolites
  • Antineoplastic Agents
  • Proliferating Cell Nuclear Antigen
  • Radiation-Sensitizing Agents
  • DNA
  • DNA Polymerase II
  • Bromodeoxyuridine
  • Nocodazole