Human DNA polymerase β initiates DNA synthesis during long-patch repair of reduced AP sites in DNA

Simple base damages are repaired through a short‐patch base excision pathway where a single damaged nucleotide is removed and replaced. DNA polymerase β (Pol β) is responsible for the repair synthesis in this pathway and also removes a 5′‐sugar phosphate residue by catalyzing a β‐elimination reactio...

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Bibliographic Details
Published in:The EMBO journal 2001-03, Vol.20 (6), p.1477-1482
Main Authors: Podlutsky, Andrej Ja, Dianova, Irina I., Podust, Vladimir N., Bohr, Vilhelm A., Dianov, Grigory L.
Format: Article
Language:English
Subjects:
AP sites
Aphidicolin - pharmacology
base excision repair
Dideoxynucleosides - pharmacology
DNA - biosynthesis
DNA - chemistry
DNA Polymerase beta - metabolism
DNA Polymerase III - metabolism
DNA polymerase β
DNA Repair - drug effects
human cell extracts
Humans
Models, Genetic
Substrate Specificity
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Summary:Simple base damages are repaired through a short‐patch base excision pathway where a single damaged nucleotide is removed and replaced. DNA polymerase β (Pol β) is responsible for the repair synthesis in this pathway and also removes a 5′‐sugar phosphate residue by catalyzing a β‐elimination reaction. How ever, some DNA lesions that render deoxyribose resistant to β‐elimination are removed through a long‐patch repair pathway that involves strand displacement synthesis and removal of the generated flap by specific endonuclease. Three human DNA polymerases (Pol β, Pol δ and Pol ϵ) have been proposed to play a role in this pathway, however the identity of the polymerase involved and the polymerase selection mechanism are not clear. In repair reactions catalyzed by cell extracts we have used a substrate containing a reduced apurinic/apyrimidinic (AP) site resistant to β‐elimination and inhibitors that selectively affect different DNA polymerases. Using this approach we find that in human cell extracts Pol β is the major DNA polymerase incorporating the first nucleotide during repair of reduced AP sites, thus initiating long‐patch base excision repair synthesis.
ISSN:0261-4189
1460-2075
DOI:10.1093/emboj/20.6.1477