Fidelity of human DNA polymerase eta - PubMed (original) (raw)
. 2000 Mar 17;275(11):7447-50.
doi: 10.1074/jbc.275.11.7447.
Affiliations
- PMID: 10713043
- DOI: 10.1074/jbc.275.11.7447
Free article
Fidelity of human DNA polymerase eta
R E Johnson et al. J Biol Chem. 2000.
Free article
Abstract
Xeroderma pigmentosum (XP) patients are highly sensitive to sunlight, and they suffer from a high incidence of skin cancers. The variant form of XP results from mutations in the hRAD30A gene, which encodes the DNA polymerase in humans, hPol(eta). Of the eukaryotic DNA polymerases, only human Pol(eta) and its yeast counterpart have the ability to replicate DNA containing a cis-syn thymine-thymine (T-T) dimer. Here we measure the fidelity of hPol(eta) on all four nondamaged template bases and at each thymine residue of a cis-syn T-T dimer. Opposite all four nondamaged template bases, hPol(eta) misincorporates nucleotides with a frequency of approximately 10(-2)-10(-3), and importantly, hPol(eta) synthesizes DNA opposite the T-T dimer with the same accuracy and efficiency as opposite the nondamaged DNA. The low fidelity of hPol(eta) may derive from a flexible active site that renders the enzyme more tolerant of geometric distortions in DNA and enables it to synthesize DNA past a T-T dimer.
Similar articles
- Mechanisms of accurate translesion synthesis by human DNA polymerase eta.
Masutani C, Kusumoto R, Iwai S, Hanaoka F. Masutani C, et al. EMBO J. 2000 Jun 15;19(12):3100-9. doi: 10.1093/emboj/19.12.3100. EMBO J. 2000. PMID: 10856253 Free PMC article. - Sequence context-dependent replication of DNA templates containing UV-induced lesions by human DNA polymerase iota.
Vaisman A, Frank EG, Iwai S, Ohashi E, Ohmori H, Hanaoka F, Woodgate R. Vaisman A, et al. DNA Repair (Amst). 2003 Sep 18;2(9):991-1006. doi: 10.1016/s1568-7864(03)00094-6. DNA Repair (Amst). 2003. PMID: 12967656 - Fidelity and processivity of Saccharomyces cerevisiae DNA polymerase eta.
Washington MT, Johnson RE, Prakash S, Prakash L. Washington MT, et al. J Biol Chem. 1999 Dec 24;274(52):36835-8. doi: 10.1074/jbc.274.52.36835. J Biol Chem. 1999. PMID: 10601233 - Replication of damaged DNA: molecular defect in xeroderma pigmentosum variant cells.
Cordonnier AM, Fuchs RP. Cordonnier AM, et al. Mutat Res. 1999 Oct 22;435(2):111-9. doi: 10.1016/s0921-8777(99)00047-6. Mutat Res. 1999. PMID: 10556591 Review. - The accurate bypass of pyrimidine dimers by DNA polymerase eta contributes to ultraviolet-induced mutagenesis.
Menck CFM, Galhardo RS, Quinet A. Menck CFM, et al. Mutat Res. 2024 Jan-Jun;828:111840. doi: 10.1016/j.mrfmmm.2023.111840. Epub 2023 Nov 7. Mutat Res. 2024. PMID: 37984186 Review.
Cited by
- Prognostic value of nucleotide excision repair and translesion DNA synthesis proteins in muscle-infiltrating bladder carcinoma.
Palacka P, Holíčková A, Roška J, Makovický P, Vallová M, Biró C, Órásová E, Obertová J, Mardiak J, Ward TA, Kajo K, Chovanec M. Palacka P, et al. BMC Cancer. 2024 Sep 5;24(1):1103. doi: 10.1186/s12885-024-12865-8. BMC Cancer. 2024. PMID: 39237917 Free PMC article. - Dynamics and thermal stability of the bypass polymerase, DinB homolog (Dbh).
Soto J, Moro SL, Cocco MJ. Soto J, et al. Front Mol Biosci. 2024 Apr 30;11:1364068. doi: 10.3389/fmolb.2024.1364068. eCollection 2024. Front Mol Biosci. 2024. PMID: 38745908 Free PMC article. - WRN exonuclease imparts high fidelity on translesion synthesis by Y family DNA polymerases.
Yoon JH, Sellamuthu K, Prakash L, Prakash S. Yoon JH, et al. Genes Dev. 2024 Apr 17;38(5-6):213-232. doi: 10.1101/gad.351410.123. Genes Dev. 2024. PMID: 38503516 Free PMC article. - High UV damage and low repair, but not cytosine deamination, stimulate mutation hotspots at ETS binding sites in melanoma.
Duan M, Song S, Wasserman H, Lee PH, Liu KJ, Gordân R, He Y, Mao P. Duan M, et al. Proc Natl Acad Sci U S A. 2024 Jan 23;121(4):e2310854121. doi: 10.1073/pnas.2310854121. Epub 2024 Jan 19. Proc Natl Acad Sci U S A. 2024. PMID: 38241433 Free PMC article. - For the Better or for the Worse? The Effect of Manganese on the Activity of Eukaryotic DNA Polymerases.
Balint E, Unk I. Balint E, et al. Int J Mol Sci. 2023 Dec 27;25(1):363. doi: 10.3390/ijms25010363. Int J Mol Sci. 2023. PMID: 38203535 Free PMC article. Review.
Publication types
MeSH terms
Substances
LinkOut - more resources
Full Text Sources
Molecular Biology Databases
Miscellaneous