Interlocking activities of DNA polymerase ß in the base excision repair pathway.
Proc Natl Acad Sci U S A
; 119(10): e2118940119, 2022 03 08.
Article
en En
| MEDLINE
| ID: mdl-35238634
SignificanceBase excision repair (BER) is one of the major DNA repair pathways used to fix a myriad of cellular DNA lesions. The enzymes involved in BER, including DNA polymerase ß (Polß), have been identified and characterized, but how they act together to efficiently perform BER has not been fully understood. Through gel electrophoresis, mass spectrometry, and kinetic analysis, we discovered that the two enzymatic activities of Polß can be interlocked, rather than functioning independently from each other, when processing DNA intermediates formed in BER. The finding prompted us to hypothesize a modified BER pathway. Through conventional and time-resolved X-ray crystallography, we solved 11 high-resolution crystal structures of cross-linked Polß complexes and proposed a detailed chemical mechanism for Polß's 5'-deoxyribose-5-phosphate lyase activity.
Palabras clave
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Daño del ADN
/
ADN Polimerasa beta
/
Reparación del ADN
Tipo de estudio:
Prognostic_studies
Idioma:
En
Revista:
Proc Natl Acad Sci U S A
Año:
2022
Tipo del documento:
Article
Pais de publicación:
Estados Unidos