Repair of UV-Induced DNA Damage Independent of Nucleotide Excision Repair Is Masked by MUTYH.
Mol Cell
; 68(4): 797-807.e7, 2017 Nov 16.
Article
en En
| MEDLINE
| ID: mdl-29149600
ABSTRACT
DNA lesions caused by UV damage are thought to be repaired solely by the nucleotide excision repair (NER) pathway in human cells. Patients carrying mutations within genes functioning in this pathway display a range of pathologies, including an increased susceptibility to cancer, premature aging, and neurological defects. There are currently no curative therapies available. Here we performed a high-throughput chemical screen for agents that could alleviate the cellular sensitivity of NER-deficient cells to UV-induced DNA damage. This led to the identification of the clinically approved anti-diabetic drug acetohexamide, which promoted clearance of UV-induced DNA damage without the accumulation of chromosomal aberrations, hence promoting cellular survival. Acetohexamide exerted this protective function by antagonizing expression of the DNA glycosylase, MUTYH. Together, our data reveal the existence of an NER-independent mechanism to remove UV-induced DNA damage and prevent cell death.
Palabras clave
Texto completo:
1
Banco de datos:
MEDLINE
Asunto principal:
Rayos Ultravioleta
/
Daño del ADN
/
ADN Glicosilasas
/
Reparación del ADN
Límite:
Humans
/
Male
Idioma:
En
Revista:
Mol Cell
Asunto de la revista:
BIOLOGIA MOLECULAR
Año:
2017
Tipo del documento:
Article
País de afiliación:
Austria