Journal
ONCOGENE
Volume 20, Issue 43, Pages 6181-6187Publisher
NATURE PUBLISHING GROUP
DOI: 10.1038/sj.onc.1204743
Keywords
DNA polymerase beta; cisplatin resistance; translesion synthesis; 6-thioguanine
Funding
- NCI NIH HHS [CA 78648] Funding Source: Medline
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DNA polymerase beta, one of the most inaccurate DNA synthesizing enzymes, has been shown to confer genetic instability when up-regulated in cells, a situation found in several human cancers. Here, we demonstrated that enhanced activity and expression of this enzyme occur in the human ovarian tumor 2008/CI3*5.25 cells, which are resistant to the antitumor agent cisplatin and hypersensitive to 6-thioguanine. We found that translesion synthesis across platinated DNA crosslinks as well as increased incorporation into DNA of 6-thioguanine took place in the 2008/CI3*5.25 cells compared to the parental 2008 cells. Such features being molecular signatures of DNA polymerase beta, these findings suggest that deregulation of its expression in cancer cells may contribute to the modulation of the response to antitumor treatments and therefore to tumor progression.
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