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Publication : Role of tyrosyl-DNA phosphodiesterase (TDP1) in mitochondria.

First Author  Das BB Year  2010
Journal  Proc Natl Acad Sci U S A Volume  107
Issue  46 Pages  19790-5
PubMed ID  21041670 Mgi Jnum  J:166601
Mgi Id  MGI:4848238 Doi  10.1073/pnas.1009814107
Citation  Das BB, et al. (2010) Role of tyrosyl-DNA phosphodiesterase (TDP1) in mitochondria. Proc Natl Acad Sci U S A 107(46):19790-5
abstractText  Human tyrosyl-DNA phosphodiesterase (TDP1) hydrolyzes the phosphodiester bond at a DNA 3'-end linked to a tyrosyl moiety and has been implicated in the repair of topoisomerase I (Top1)-DNA covalent complexes. TDP1 can also hydrolyze other 3'-end DNA alterations including 3'-phosphoglycolate and 3'-abasic sites, and exhibits 3'-nucleosidase activity indicating it may function as a general 3'-end-processing DNA repair enzyme. Here, using laser confocal microscopy, subcellular fractionation and biochemical analyses we demonstrate that a fraction of the TDP1 encoded by the nuclear TDP1 gene localizes to mitochondria. We also show that mitochondrial base excision repair depends on TDP1 activity and provide evidence that TDP1 is required for efficient repair of oxidative damage in mitochondrial DNA. Together, our findings provide evidence for TDP1 as a novel mitochondrial enzyme.
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