Mutation spectra induced by adozelesin in the supF gene of human XP-A fibroblasts.

Arch Pharm Res

School of Biotechnology, Yeungnam University, Gyeongsan, 712-749, Korea.

Published: April 2010

AI Article Synopsis

  • Adozelesin is a synthetic version of the antitumor antibiotic CC-1065, known for its ability to target DNA by alkylating adenine in a specific sequence.
  • The study tested how adozelesin caused mutations in the supF gene of XP-A human fibroblasts and found that the primary mutation types were A --> T transversions and single base insertions.
  • The A --> T transversion occurred mostly at the site of alkylation, while single base insertions were found near the modified adenine, indicating that the way adozelesin interacts with DNA influences the mutations it causes.

Article Abstract

Adozelesin is a synthetic analog of the antitumor antibiotic, CC-1065, which alkylates N3 of adenine in the minor DNA groove in a sequence-specific manner. Here we tested the mutation spectra induced by adozelesin in the supF gene of human XP-A fibroblasts using a shuttle vector assay. Adozelesin primarily induces mutations via an A --> T transversion and a single base insertion. The A --> T transversion (43/59) was observed at the adenine alkylation site in the 5'-ATTTA* sequence (A* is the site of alkylation). The single base insertion (5/59) was observed at the 3'-side of the covalently modified adenine in the 5'-CTAAA* sequence. The results of this study suggest that the DNA alkylating sequence of adozelesin influences the type of DNA mutation.

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http://dx.doi.org/10.1007/s12272-010-0419-7DOI Listing

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