Oxidant and environmental toxicant-induced effects compromise DNA ligation during base excision DNA repair.
DNA Repair (Amst)
; 35: 85-9, 2015 Nov.
Article
en En
| MEDLINE
| ID: mdl-26466358
ABSTRACT
DNA lesions arise from many endogenous and environmental agents, and such lesions can promote deleterious events leading to genomic instability and cell death. Base excision repair (BER) is the main DNA repair pathway responsible for repairing single strand breaks, base lesions and abasic sites in mammalian cells. During BER, DNA substrates and repair intermediates are channeled from one step to the next in a sequential fashion so that release of toxic repair intermediates is minimized. This includes handoff of the product of gap-filling DNA synthesis to the DNA ligation step. The conformational differences in DNA polymerase ß (pol ß) associated with incorrect or oxidized nucleotide (8-oxodGMP) insertion could impact channeling of the repair intermediate to the final step of BER, i.e., DNA ligation by DNA ligase I or the DNA Ligase III/XRCC1 complex. Thus, modified DNA ligase substrates produced by faulty pol ß gap-filling could impair coordination between pol ß and DNA ligase. Ligation failure is associated with 5'-AMP addition to the repair intermediate and accumulation of strand breaks that could be more toxic than the initial DNA lesions. Here, we provide an overview of the consequences of ligation failure in the last step of BER. We also discuss DNA-end processing mechanisms that could play roles in reversal of impaired BER.
Palabras clave
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
ADN Ligasas
/
Daño del ADN
/
Sustancias Peligrosas
/
Oxidantes
/
ADN Polimerasa beta
/
Desoxiguanosina
/
Reparación del ADN
Tipo de estudio:
Risk_factors_studies
Límite:
Humans
Idioma:
En
Revista:
DNA Repair (Amst)
Asunto de la revista:
BIOLOGIA MOLECULAR
/
BIOQUIMICA
Año:
2015
Tipo del documento:
Article
País de afiliación:
Estados Unidos