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Misinsertion and bypass of thymine–thymine dimers by human DNA polymerase ι
Author(s) -
Tissier Agnès,
Frank Ekaterina G.,
McDonald John P.,
Iwai Shigenori,
Hanaoka Fumio,
Woodgate Roger
Publication year - 2000
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/19.19.5259
Subject(s) - pyrimidine dimer , thymine , biology , dna , polymerase , dna polymerase , pyrimidine , dna damage , nucleotide , dna replication , microbiology and biotechnology , stereochemistry , biophysics , biochemistry , chemistry , gene
Human DNA polymerase ι (polι) is a recently discovered enzyme that exhibits extremely low fidelity on undamaged DNA templates. Here, we show that polι is able to facilitate limited translesion replication of a thymine–thymine cyclobutane pyrimidine dimer (CPD). More importantly, however, the bypass event is highly erroneous. Gel kinetic assays reveal that polι misinserts T or G opposite the 3′ T of the CPD ∼1.5 times more frequently than the correct base, A. While polι is unable to extend the T·T mispair significantly, the G·T mispair is extended and the lesion completely bypassed, with the same efficiency as that of the correctly paired A·T base pair. By comparison, polι readily misinserts two bases opposite a 6‐4 thymine–thymine pyrimidine–pyrimidone photoproduct (6‐4PP), but complete lesion bypass is only a fraction of that observed with the CPD. Our data indicate, therefore, that polι possesses the ability to insert nucleotides opposite UV photoproducts as well as to perform unassisted translesion replication that is likely to be highly mutagenic.