[PMID]: | 28459528 |
[Au] Autor: | Laverty DJ; Averill AM; Doublié S; Greenberg MM |
[Ad] Endereço: | Department of Chemistry, Johns Hopkins University , 3400 N. Charles St., Baltimore, Maryland 21218, United States. |
[Ti] Título: | The A-Rule and Deletion Formation During Abasic and Oxidized Abasic Site Bypass by DNA Polymerase θ. |
[So] Source: | ACS Chem Biol;12(6):1584-1592, 2017 06 16. |
[Is] ISSN: | 1554-8937 |
[Cp] País de publicação: | United States |
[La] Idioma: | eng |
[Ab] Resumo: | DNA polymerase θ (Pol θ) is implicated in various cellular processes including double-strand break repair and apurinic/apyrimidinic site bypass. Because Pol θ expression correlates with poor cancer prognosis, the ability of Pol θ to bypass the C4'-oxidized abasic site (C4-AP) and 2-deoxyribonolactone (L), which are generated by cytotoxic agents, is of interest. Translesion synthesis and subsequent extension by Pol θ past C4-AP or L and an abasic site (AP) or its tetrahydrofuran analogue (F) was examined. Pol θ conducts translesion synthesis on templates containing AP and F with similar efficiencies and follows the "A-rule," inserting nucleotides in the order A > G > T. Translesion synthesis on templates containing C4-AP and L is less efficient than AP and F, and the preference for A insertion is reduced for L and absent for C4-AP. Extension past all abasic lesions (AP, F, C4-AP, and L) was significantly less efficient than translesion synthesis and yielded deletions caused by the base one or two nucleotides downstream from the lesion being used as a template, with the latter being favored. These results suggest that bypass of abasic lesions by Pol θ is highly mutagenic. |
[Mh] Termos MeSH primário: |
DNA Polimerase beta/fisiologia Mutagênese
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[Mh] Termos MeSH secundário: |
Animais Sequência de Bases Dano ao DNA DNA Polimerase beta/metabolismo Reparo do DNA Seres Humanos Nucleotídeos/metabolismo Oxirredução Deleção de Sequência Açúcares Ácidos Moldes Genéticos
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[Pt] Tipo de publicação: | JOURNAL ARTICLE; RESEARCH SUPPORT, N.I.H., EXTRAMURAL |
[Nm] Nome de substância:
| 0 (Nucleotides); 0 (Sugar Acids); 34371-14-7 (2,4,5-trihydroxypentanoic acid gamma-lactone); EC 2.7.7.- (DNA Polymerase beta) |
[Em] Mês de entrada: | 1709 |
[Cu] Atualização por classe: | 180201 |
[Lr] Data última revisão:
| 180201 |
[Sb] Subgrupo de revista: | IM |
[Da] Data de entrada para processamento: | 170502 |
[St] Status: | MEDLINE |
[do] DOI: | 10.1021/acschembio.7b00211 |
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