4.8 Article

Mutagenic effects of abasic and oxidized abasic lesions in Saccharomyces cerevisiae

Journal

NUCLEIC ACIDS RESEARCH
Volume 33, Issue 19, Pages 6196-6202

Publisher

OXFORD UNIV PRESS
DOI: 10.1093/nar/gki926

Keywords

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Funding

  1. NATIONAL CANCER INSTITUTE [R56CA090860, R01CA090860] Funding Source: NIH RePORTER
  2. NATIONAL INSTITUTE OF ENVIRONMENTAL HEALTH SCIENCES [P01ES011163] Funding Source: NIH RePORTER
  3. NATIONAL INSTITUTE OF GENERAL MEDICAL SCIENCES [R01GM064769, R01GM063028] Funding Source: NIH RePORTER
  4. NCI NIH HHS [CA90860, R01 CA090860, R56 CA090860] Funding Source: Medline
  5. NIEHS NIH HHS [P01 ES011163] Funding Source: Medline
  6. NIGMS NIH HHS [R01 GM063028, R01 GM064769, GM63028, GM64769] Funding Source: Medline

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2-Deoxyribonolactone (L) and 2-deoxyribose (AP) are abasic sites that are produced by ionizing radiation, reactive oxygen species and a variety of DNA damaging agents. The biological processing of the AP site has been examined in the yeast Saccharomyces cerevisiae. However, nothing is known about how L is processed in this organism. We determined the bypass and mutagenic specificity of DNA containing an abasic site (AP and L) or the AP analog tetrahydrofuran (F) using an oligonucleotide transformation assay. The tetrahydrofuran analog and L were bypassed at 10-fold higher frequencies than the AP lesions. Bypass frequencies of lesions were greatly reduced in the absence of Rev1 or Pol zeta (rev3 mutant), but were only marginally reduced in the absence of Pol eta (rad30 mutant). Deoxycytidine was the preferred nucleotide inserted opposite an AP site whereas dA and dC were inserted at equal frequencies opposite F and L sites. In the rev1 and rev3 strains, dA was the predominant nucleotide inserted opposite these lesions. Overall, we conclude that both Rev1 and Pol zeta are required for the efficient bypass of abasic sites in yeast.

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