Interaction of Human DNA Polymerase η with Monoubiquitinated PCNA: A Possible Mechanism for the Polymerase Switch in Response to DNA Damage

Kannouche, Patricia L, Wing, Jonathan and Lehmann, Alan R (2004) Interaction of Human DNA Polymerase η with Monoubiquitinated PCNA: A Possible Mechanism for the Polymerase Switch in Response to DNA Damage. Molecular Cell, 14 (4). pp. 491-500. ISSN 1097-2765

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Abstract

Most types of DNA damage block replication fork progression during DNA synthesis because replicative DNA polymerases are unable to accommodate altered DNA bases in their active sites. To overcome this block, eukaryotic cells employ specialized translesion synthesis (TLS) polymerases, which can insert nucleotides opposite damaged bases. In particular, TLS by DNA polymerase ¿ (pol¿) is the major pathway for bypassing UV photoproducts. How the cell switches from replicative to TLS polymerase at the site of blocked forks is unknown. We show that, in human cells, PCNA becomes monoubiquitinated following UV irradiation of the cells and that this is dependent on the hRad18 protein. Monoubiquitinated PCNA but not unmodified PCNA specifically interacts with pol¿, and we have identified two motifs in pol¿ that are involved in this interaction. Our findings provide an attractive mechanism by which monoubiquitination of PCNA might mediate the polymerase switch.

Item Type: Article
Additional Information: All done in my lab. Paper provided insight into mechanism of switching from replicative to bypass polymerase at sites of DNA damage in human cells.
Schools and Departments: School of Life Sciences > Sussex Centre for Genome Damage and Stability
Depositing User: Jonathan Wing
Date Deposited: 06 Feb 2012 20:42
Last Modified: 02 Apr 2012 14:06
URI: http://srodev.sussex.ac.uk/id/eprint/27617
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