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Conversion of Phosphoglycolate to Phosphate Termini on 3′ Overhangs of DNA Double Strand Breaks by the Human Tyrosyl-DNA Phosphodiesterase hTdp1
Open accessAbstract
Mammalian cells contain potent activity for removal of 3'-phosphoglycolates from single-stranded oligomers and from 3' overhangs of DNA double strand breaks, but no specific enzyme has been implicated in such removal. Fractionated human whole-cell extracts contained an activity, which in the presence of EDTA, catalyzed removal of glycolate from phosphoglycolate at a single-stranded 3' terminus to leave a 3'-phosphate, reminiscent of the human tyrosyl-DNA phosphodiesterase hTdp1. Recombinant hTdp1, as well as Saccharomyces cerevisiae Tdp1, catalyzed similar removal of glycolate, although less efficiently than removal of tyrosine. Moreover, glycolate-removing activity could be immunodepleted from the fractionated extracts by antiserum to hTdp1. When a plasmid containing a double strand break with a 3'-phosphoglycolate on a 3-base 3' overhang was incubated in human cell extracts, phosphoglycolate processing proceeded rapidly for the first few minutes but then slowed dramatically, suggesting that the single-stranded overhangs gradually became sequestered and inaccessible to hTdp1. The results suggest a role for hTdp1 in repair of free radical-mediated DNA double strand breaks bearing terminally blocked 3' overhangs.
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Cites
gamma Ray induced deoxyribonucleic acid strand breaks. 3' Glycolate termini.
Henner, W. D., Rodriguez, L. O., Hecht, S. M., & Haseltine, W. A. (1983) · Journal of Biological Chemistry · doi:10.1016/s0021-9258(18)33104-1 · Cited by 325
DNA end-joining catalyzed by human cell-free extracts
Baumann, P., & West, S. C. (1998) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.95.24.14066 · Cited by 295
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Metadata
- Authors
- Inamdar, K. V., Pouliot, J. J., Zhou, T., Lees-Miller, S. P., Rasouli-Nia, A., & Povirk, L. F.
- Venue
- Journal of Biological Chemistry
- Publisher
- Elsevier BV
- Published
- 2002-07
- Volume
- 277
- Issue
- 30
- Pages
- 27162-27168
- ISSN
- 0021-9258 (ISSN-L)
- OpenAlex
- W2114507050
- Cited by
- 199
- References
- 2
- FWCI
- 4.10
- Type
- journal article
- Language
- en
- Open access
- hybrid
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- The paper
- Inamdar, K. V., Pouliot, J. J., Zhou, T., Lees-Miller, S. P., Rasouli-Nia, A., & Povirk, L. F. (2002). Conversion of Phosphoglycolate to Phosphate Termini on 3′ Overhangs of DNA Double Strand Breaks by the Human Tyrosyl-DNA Phosphodiesterase hTdp1. Journal of Biological Chemistry. https://doi.org/10.1074/jbc.m204688200
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Contains information from the Semantic Scholar Academic Graph Datasets, made available under the ODC Attribution License (ODC-BY 1.0).
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