| Autor: |
Kusumoto, Rika, Masutani, Chikahide, Shimmyo, Shizu, Iwai, Shigenori, Hanaoka, Fumio |
| Předmět: |
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| Zdroj: |
Genes to Cells; Dec2004, Vol. 9 Issue 12, p1139-1150, 12p |
| Abstrakt: |
The human XPV (xeroderma pigmentosum variant) gene is responsible for the cancer–prone xeroderma pigmentosum syndrome and encodes DNA polymeraseη (polη), which catalyses efficient translesion synthesis pastcis-syn cyclobutane thymine dimers (TT dimers) and other lesions. The fidelity of DNA synthesis by polη on undamaged templates is extremely low, suggesting that polη activity must be restricted to damaged sites on DNA. Little is known, however, about how the activity of polη is targeted and restricted to damaged DNA. Here we show that polη binds template/primer DNAs regardless of the presence of TT dimers. Rather, enhanced binding to template/primer DNAs containing TT dimers is only observed when the 3′-end of the primer is an adenosine residue situated opposite the lesion. When two nucleotides have been incorporated into the primer beyond the TT dimer position, the polη-template/primer DNA complex is destabilized, allowing DNA synthesis by DNA polymerasesα orδ to resume. Our study provides mechanistic explanations for polymerase switching at TT dimer sites. [ABSTRACT FROM AUTHOR] |
| Databáze: |
Complementary Index |
| Externí odkaz: |
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