Premium
Unique misinsertion specificity of polι may decrease the mutagenic potential of deaminated cytosines
Author(s) -
Vaisman Alexandra,
Woodgate Roger
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/20.22.6520
Subject(s) - uracil , cytosine , biology , deamination , guanine , nucleotide , dna , biochemistry , dna polymerase , dna replication , base pair , microbiology and biotechnology , enzyme , gene
DNA polymerase ι (polι) is a distributive error‐prone enzyme that can incorporate nucleotides opposite a variety of DNA lesions. Further elongation is, however, either substantially inhibited or completely abolished. Here, we provide evidence that polι can facilitate the efficient bypass of uracil and its derivatives as well as oxidized cytosine and guanine residues. The fidelity of translesion replication depends upon the lesion encountered. Correct nucleotides were inserted preferentially opposite 7,8‐dihydro‐8‐oxoguanine (8‐oxoG) and 5‐hydroxycytosine (5‐OHC). However, when bypassing uracil, 5‐hydroxyuracil (5‐OHU) or 5,6‐dihydrouracil (5,6‐DHU), polι inserted T and G with a 4‐ to 26‐fold preference over the Watson—Crick base, A. While the T:U, T:5‐OHU and T:5,6‐DHU mispairs were extended poorly, the G:U, G:5‐OHU and G:5,6‐DHU mispairs were extended with equal or greater efficiency than the correctly paired primer termini. Thus, polι‐dependent misinsertion of G opposite uracil and its derivatives may actually provide a mechanism whereby mammalian cells can decrease the mutagenic potential of lesions formed via the deamination of cytosine.