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Human DNA polymerase β initiates DNA synthesis during long‐patch repair of reduced AP sites in DNA
Author(s) -
Podlutsky Andrej Ja.,
Dianova Irina I.,
Podust Vladimir N.,
Bohr Vilhelm A.,
Dianov Grigory L.
Publication year - 2001
Publication title -
the embo journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 7.484
H-Index - 392
eISSN - 1460-2075
pISSN - 0261-4189
DOI - 10.1093/emboj/20.6.1477
Subject(s) - base excision repair , dna polymerase , ap site , biology , dna polymerase ii , dna polymerase beta , dna polymerase delta , ap endonuclease , dna clamp , processivity , polymerase , dna repair , dna polymerase mu , microbiology and biotechnology , nucleotide excision repair , dna glycosylase , dna polymerase i , dna (apurinic or apyrimidinic site) lyase , dna , biochemistry , circular bacterial chromosome , polymerase chain reaction , reverse transcriptase , gene
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.