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J. Biol. Chem., Vol. 277, Issue 52, 50487-50490, December 27, 2002

This Article Full Text Full Text (PDF) All Versions of this Article: 277/52/50487    most recent M208153200v1 Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Elder, R. H. Articles by Dianov, G. L. Search for Related Content PubMed PubMed Citation Articles by Elder, R. H. Articles by Dianov, G. L.

Repair of Dihydrouracil Supported by Base Excision Repair in mNTH1 Knock-out Cell Extracts^*

Rhoderick H. Elder and Grigory L. Dianov^§¶

From the ^§ Medical Research Council Radiation and Genome Stability Unit, Harwell, Oxfordshire, OX11 0RD, United Kingdom and  Cancer Research UK, Carcinogenesis Group, Paterson Institute for Cancer Research, Christie Hospital National Health Service Trust, Manchester, M20 4BX, United Kingdom

In mammalian cells, thymine glycols and other oxidized pyrimidines such as 5,6-dihydrouracil are removed from DNA by the NTH1 protein, a bifunctional DNA-N-glycosylase. However, mNTH1 knock-out mice in common with other DNA glycosylase-deficient mice do not show any severe abnormalities associated with accumulation of DNA damage and mutations. In the present study we used an in vitro repair system to investigate the mechanism for the removal of 5,6-dihydrouracil from DNA by mNTH1-deficient cell-free extracts derived from testes of mNTH1 knock-out mice. We found that these extracts are able to support the removal of 5,6-dihydrouracil from DNA at about 20% of the efficiency of normal extracts. Furthermore, we also found that single-nucleotide patch base excision repair is the major pathway for removal of 5,6-dihydrouracil in mNTH1-deficient cell extracts, suggesting the involvement of other DNA glycosylase(s) in the removal of oxidized pyrimidines.

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