QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

Vol. 19, Issue 12, 5193-5202, December 2008

This Article Full Text Full Text (PDF) Supplemental Materials All Versions of this Article: E08-07-0724v1 19/12/5193    most recent Alert me when this article is cited Alert me if a correction is posted Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Sabbioneda, S. Articles by Lehmann, A. R. Search for Related Content PubMed PubMed Citation Articles by Sabbioneda, S. Articles by Lehmann, A. R.

Effect of Proliferating Cell Nuclear Antigen Ubiquitination and Chromatin Structure on the Dynamic Properties of the Y-family DNA Polymerases

Simone Sabbioneda^*, Audrey M. Gourdin, Catherine M. Green^*,, Angelika Zotter, Giuseppina Giglia-Mari, Adriaan Houtsmuller, Wim Vermeulen, and Alan R. Lehmann^*

*Genome Damage and Stability Centre, University of Sussex, Falmer, Brighton BN1 9RQ, United Kingdom; and MGC Department of Genetics and Cell Biology and Department of Pathology, Erasmus Medical Center, 3000 DR Rotterdam, The Netherlands

Submitted July 15, 2008; Revised August 19, 2008; Accepted September 8, 2008
Monitoring Editor: Orna Cohen-Fix

Y-family DNA polymerases carry out translesion synthesis past damaged DNA. DNA polymerases (pol) and are usually uniformly distributed through the nucleus but accumulate in replication foci during S phase. DNA-damaging treatments result in an increase in S phase cells containing polymerase foci. Using photobleaching techniques, we show that pol is highly mobile in human fibroblasts. Even when localized in replication foci, it is only transiently immobilized. Although ubiquitination of proliferating cell nuclear antigen (PCNA) is not required for the localization of pol in foci, it results in an increased residence time in foci. pol is even more mobile than pol, both when uniformly distributed and when localized in foci. Kinetic modeling suggests that both pol and pol diffuse through the cell but that they are transiently immobilized for 150 ms, with a larger proportion of pol than pol immobilized at any time. Treatment of cells with DRAQ5, which results in temporary opening of the chromatin structure, causes a dramatic immobilization of pol but not pol. Our data are consistent with a model in which the polymerases are transiently probing the DNA/chromatin. When DNA is exposed at replication forks, the polymerase residence times increase, and this is further facilitated by the ubiquitination of PCNA.

Present address: Department of Zoology, University of Cambridge, Cambridge CB2 3EJ, United Kingdom.

Address correspondence to: Alan R. Lehmann (a.r.lehmann{at}sussex.ac.uk)

This article has been cited by other articles:

				L. S. Waters, B. K. Minesinger, M. E. Wiltrout, S. D'Souza, R. V. Woodruff, and G. C. Walker Eukaryotic Translesion Polymerases and Their Roles and Regulation in DNA Damage Tolerance Microbiol. Mol. Biol. Rev., March 1, 2009; 73(1): 134 - 154. [Abstract] [Full Text] [PDF]

				S. Sabbioneda, C. M. Green, M. Bienko, P. Kannouche, I. Dikic, and A. R. Lehmann Ubiquitin-binding motif of human DNA polymerase {eta} is required for correct localization PNAS, February 24, 2009; 106(8): E20 - E20. [Full Text] [PDF]