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Originally published In Press as doi:10.1074/jbc.M110615200 on December 10, 2001

J. Biol. Chem., Vol. 277, Issue 10, 8658-8666, March 8, 2002
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Human DNA Polymerase epsilon  Colocalizes with Proliferating Cell Nuclear Antigen and DNA Replication Late, but Not Early, in S Phase*,

Jill FussDagger and Stuart Linn§

From the Department of Molecular and Cell Biology, Division of Biochemistry and Molecular Biology, University of California, Berkeley, California 94720-3206

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 G1 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.


* This work was supported by National Institutes of Health Grants 1RO1GM30415 and P30ES08196.The costs of publication of this article were defrayed in part by the payment of page charges. The article must therefore be hereby marked "advertisement" in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

The on-line version of this article (available at http://www.jbc.org) contains a supplemental video which shows a series of confocal planes that progress from the lower to the uppermost planes of the cells shown in Fig. 5. A mitotic (upper right) and an S phase (lower left) cell are stained for pol epsilon  p261 (red), BrdUrd (green), and DAPI (blue).

Dagger Current address: Lawrence Berkeley National Laboratory, 1 Cyclotron Road, MS 74-157, Berkeley, CA 94720.

§ To whom correspondence should be addressed: Dept. of Molecular and Cell Biology, Division of Biochemistry and Molecular Biology, 229 Stanley Hall, University of California, Berkeley, CA 94720-3206. Tel.: 510-642-7583; Fax: 510-643-9290; E-mail: slinn@socrates.berkeley.edu.


Copyright © 2002 by The American Society for Biochemistry and Molecular Biology, Inc.


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