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An Unexpectedly High Excision Capacity for Mispaired 5-Hydroxymethyluracil in Human Cell Extracts

Valaiporn Rusmintratip and Lawrence C. Sowers
Proceedings of the National Academy of Sciences of the United States of America
Vol. 97, No. 26 (Dec. 19, 2000), pp. 14183-14187
Stable URL: http://www.jstor.org/stable/2666269
Page Count: 5
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Since scans are not currently available to screen readers, please contact JSTOR User Support for access. We'll provide a PDF copy for your screen reader.
An Unexpectedly High Excision Capacity for Mispaired 5-Hydroxymethyluracil in Human Cell Extracts
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Abstract

The oxidation of thymine in DNA can generate a base pair between 5-hydroxymethyluracil (HmU) and adenine, whereas the oxidation and deamination of 5-methylcytosine (5mC) in DNA can generate a base pair between HmU and guanine. Using synthetic oligonucleotides containing HmU at a defined site, HmU-DNA glycosylase activities in HeLa cell and human fibroblast cell extracts have been observed. An HmU-DNA glycosylase activity that removes HmU mispaired with guanine has been measured. Surprisingly, the HmU:G excision activity is 60 times greater than the corresponding HmU:A activity, even though the expected rate of formation of the HmU:A base pair exceeds that of the HmU:G base pair by a factor of 107. The HmU:G mispair would arise from the 5mC:G base pair, and, if unrepaired, would give rise to a transition mutation. The observation of an unexpectedly high HmU:G glycosylase activity suggests that human cells may encounter the HmU:G mispair much more frequently than expected. The conversion of 5mC to HmU must be considered as a potential pathway for the generation of 5mC to T transition mutations, which are often found in human tumors.

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