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Inhibition of DNA polymerase activity by thymine hydrates.
Mutat Res. 1992 Nov; 293(1):71-7.MR

Abstract

Ultraviolet irradiation of DNA results in various pyrimidine modifications. We have demonstrated formation of both cis-thymine hydrate and trans-thymine hydrate (6-hydroxy-5,6-dihydrothymine) in UV-irradiated poly(dA-dT):poly(dA-dT). Both are released from DNA as free bases by bacterial and human glycosylases. Thymine hydrates are stable in DNA and can be detected in control, unirradiated substrates. We examined the effects of thymine hydrates in UV-irradiated substrate poly(dA-dT):poly(dA-dT) on E. coli DNA polymerase I activity. Enzymic incorporation of labeled thymidine-5'-monophosphate significantly decreased with increasing UV dose. Reversal of DNA thymine hydrates to thymines by mild heating of the substrate prior to enzymic reaction resulted in partial recovery of nucleotide incorporation. Cyclobutane thymine dimers are formed between non-adjacent thymines in UV-irradiated poly(dA-dT):poly(dA-dT). These are responsible for the incomplete recovery of DNA polymerase activity following heating due to their heat stability. Analyses of the irradiated and hydrolyzed substrate also demonstrated formation of minor yields of photoproducts formed by covalent linkage of adjacent thymines and adenines by UV-irradiation. Therefore, the thymine hydrates formed in UV-irradiated DNA partially inhibit polymerase activity during DNA synthesis and thus could be potentially lethal if unrepaired.

Authors+Show Affiliations

Department of Pathology, Temple University School of Medicine, Philadelphia, PA 19140.No affiliation info available

Pub Type(s)

Journal Article
Research Support, U.S. Gov't, P.H.S.

Language

eng

PubMed ID

1383813

Citation

Ganguly, T, and N J. Duker. "Inhibition of DNA Polymerase Activity By Thymine Hydrates." Mutation Research, vol. 293, no. 1, 1992, pp. 71-7.
Ganguly T, Duker NJ. Inhibition of DNA polymerase activity by thymine hydrates. Mutat Res. 1992;293(1):71-7.
Ganguly, T., & Duker, N. J. (1992). Inhibition of DNA polymerase activity by thymine hydrates. Mutation Research, 293(1), 71-7.
Ganguly T, Duker NJ. Inhibition of DNA Polymerase Activity By Thymine Hydrates. Mutat Res. 1992;293(1):71-7. PubMed PMID: 1383813.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Inhibition of DNA polymerase activity by thymine hydrates. AU - Ganguly,T, AU - Duker,N J, PY - 1992/11/1/pubmed PY - 1992/11/1/medline PY - 1992/11/1/entrez SP - 71 EP - 7 JF - Mutation research JO - Mutat. Res. VL - 293 IS - 1 N2 - Ultraviolet irradiation of DNA results in various pyrimidine modifications. We have demonstrated formation of both cis-thymine hydrate and trans-thymine hydrate (6-hydroxy-5,6-dihydrothymine) in UV-irradiated poly(dA-dT):poly(dA-dT). Both are released from DNA as free bases by bacterial and human glycosylases. Thymine hydrates are stable in DNA and can be detected in control, unirradiated substrates. We examined the effects of thymine hydrates in UV-irradiated substrate poly(dA-dT):poly(dA-dT) on E. coli DNA polymerase I activity. Enzymic incorporation of labeled thymidine-5'-monophosphate significantly decreased with increasing UV dose. Reversal of DNA thymine hydrates to thymines by mild heating of the substrate prior to enzymic reaction resulted in partial recovery of nucleotide incorporation. Cyclobutane thymine dimers are formed between non-adjacent thymines in UV-irradiated poly(dA-dT):poly(dA-dT). These are responsible for the incomplete recovery of DNA polymerase activity following heating due to their heat stability. Analyses of the irradiated and hydrolyzed substrate also demonstrated formation of minor yields of photoproducts formed by covalent linkage of adjacent thymines and adenines by UV-irradiation. Therefore, the thymine hydrates formed in UV-irradiated DNA partially inhibit polymerase activity during DNA synthesis and thus could be potentially lethal if unrepaired. SN - 0027-5107 UR - https://www.unboundmedicine.com/medline/citation/1383813/Inhibition_of_DNA_polymerase_activity_by_thymine_hydrates_ L2 - https://linkinghub.elsevier.com/retrieve/pii/0921-8777(92)90010-Z DB - PRIME DP - Unbound Medicine ER -