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Recruitment of RNA polymerase II cofactor PC4 to DNA damage sites.

Mortusewicz, Oliver and Roth, Wera and Li, Na and Cardoso, M Cristina and Meisterernst, Michael and Leonhardt, Heinrich (2008):
Recruitment of RNA polymerase II cofactor PC4 to DNA damage sites.
In: The Journal of cell biology, pp. 769-76, 183, (5), ISSN 1540-8140,
[Online-Edition: http://www.cardoso-lab.org/publications/Mortusewicz_2008b.pd...],
[Article]

Abstract

The multifunctional nuclear protein positive cofactor 4 (PC4) is involved in various cellular processes including transcription, replication, and chromatin organization. Recently, PC4 has been identified as a suppressor of oxidative mutagenesis in Escherichia coli and Saccharomyces cerevisiae. To investigate a potential role of PC4 in mammalian DNA repair, we used a combination of live cell microscopy, microirradiation, and fluorescence recovery after photobleaching analysis. We found a clear accumulation of endogenous PC4 at DNA damage sites introduced by either chemical agents or laser microirradiation. Using fluorescent fusion proteins and specific mutants, we demonstrated that the rapid recruitment of PC4 to laser-induced DNA damage sites is independent of poly(ADP-ribosyl)ation and gammaH2AX but depends on its single strand binding capacity. Furthermore, PC4 showed a high turnover at DNA damages sites compared with the repair factors replication protein A and proliferating cell nuclear antigen. We propose that PC4 plays a role in the early response to DNA damage by recognizing single-stranded DNA and may thus initiate or facilitate the subsequent steps of DNA repair.

Item Type: Article
Erschienen: 2008
Creators: Mortusewicz, Oliver and Roth, Wera and Li, Na and Cardoso, M Cristina and Meisterernst, Michael and Leonhardt, Heinrich
Title: Recruitment of RNA polymerase II cofactor PC4 to DNA damage sites.
Language: English
Abstract:

The multifunctional nuclear protein positive cofactor 4 (PC4) is involved in various cellular processes including transcription, replication, and chromatin organization. Recently, PC4 has been identified as a suppressor of oxidative mutagenesis in Escherichia coli and Saccharomyces cerevisiae. To investigate a potential role of PC4 in mammalian DNA repair, we used a combination of live cell microscopy, microirradiation, and fluorescence recovery after photobleaching analysis. We found a clear accumulation of endogenous PC4 at DNA damage sites introduced by either chemical agents or laser microirradiation. Using fluorescent fusion proteins and specific mutants, we demonstrated that the rapid recruitment of PC4 to laser-induced DNA damage sites is independent of poly(ADP-ribosyl)ation and gammaH2AX but depends on its single strand binding capacity. Furthermore, PC4 showed a high turnover at DNA damages sites compared with the repair factors replication protein A and proliferating cell nuclear antigen. We propose that PC4 plays a role in the early response to DNA damage by recognizing single-stranded DNA and may thus initiate or facilitate the subsequent steps of DNA repair.

Journal or Publication Title: The Journal of cell biology
Volume: 183
Number: 5
Divisions: 10 Department of Biology > Cell Biology and Epigenetics
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10 Department of Biology
Date Deposited: 06 Mar 2010 16:05
Official URL: http://www.cardoso-lab.org/publications/Mortusewicz_2008b.pd...
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