Polymerase-tautomeric Model for Untargeted Delayed Base Substitution Mutations Formation during Error-prone and SOS Replication of Double-stranded DNA Containing Thymine and Adenine in Some Rare Tautomeric Forms

• 作者: Helen A.Grebneva
• 来源期刊: 肿瘤学研究(英文)
• 学科: 化学
• 关键词: Radiation-induced genomic instability Untargeted DELAYED base substitution MUTATIONS UV-mutagenesis Rare tautomeric forms of DNA bases Thymine adenine ERROR-PRONE REPLICATION SOS REPLICATION
• 年，卷（期）: 2019,（2）
• 页码范围: 24-37
• 页数: 14页
• 分类号: O62

摘要

Polymerase-tautomeric model for untargeted delayed base substitution mutations is proposed.Structural analysis of bases insertion showed that any canonical bases may be inserted opposite rare tautomeric forms of thymine T3*,adenines A2*and A4*so that between them hydrogen bonds are formed.Canonical adenine and cytosine can be incorporated opposite canonical thymine only.Canonical thymine and guanine can be incorporated opposite canonical adenine only.If in the synthesis of DNA containing rare tautomeric forms of thymine T3*,adenines A2*and A4*,involved DNA polymerases with relatively high fidelity of synthesis,mutations not appear.However,if further DNA synthesis will involve DNA polymerases having a low fidelity of synthesis,there may be base substitution mutations.It was shown that the conclusion made in the Tomasetti and Vogelstein cancer risk model that the formation of about 67%of all mutations was not caused by exposure to any mutagens is erroneous.