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EMBO J. 2004 Oct 27;23(21):4342-52. Epub 2004 Oct 7.

Defining the position of the switches between replicative and bypass DNA polymerases.

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  • 1UPR 9003 du CNRS, Cancerogenese et Mutagenese Moleculaire et Structurale, ESBS Pole API, Blvd S Brant Strasbourg, 67400 Illkirch-Graffenstaden, France.

Abstract

Cells contain specialized DNA polymerases that are able to copy past lesions with an associated risk of generating mutations, the major cause of cancer. Here, we reconstitute translesion synthesis (TLS) using the replicative (Pol III) and major bypass (Pol V) DNA polymerases from Escherichia coli in the presence of accessory factors. When the replicative polymerase disconnects from the template in the vicinity of a lesion, Pol V binds the blocked replication intermediate and forms a stable complex by means of a dual interaction with the tip of the RecA filament and the beta-clamp, the processivity factor donated by the blocked Pol III holoenzyme. Both interactions are required to confer to Pol V the processivity that will allow it synthesize, in a single binding event, a TLS patch long enough to support further extension by Pol III. In the absence of these accessory factors, the patch synthesized by Pol V is too short, being degraded by the Pol III-associated exonuclease activity that senses the distortion induced by the lesion, thus leading to an aborted bypass process.

PMID:
15470496
[PubMed - indexed for MEDLINE]
PMCID:
PMC524402
Free PMC Article
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