Repair of UV-Induced DNA Damage Independent of Nucleotide Excision Repair Is Masked by MUTYH.

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.

journal_name

Mol Cell

journal_title

Molecular cell

authors

Mazouzi A,Battistini F,Moser SC,Ferreira da Silva J,Wiedner M,Owusu M,Lardeau CH,Ringler A,Weil B,Neesen J,Orozco M,Kubicek S,Loizou JI

doi

10.1016/j.molcel.2017.10.021

subject

Has Abstract

pub_date

2017-11-16 00:00:00

pages

797-807.e7

issue

4

eissn

1097-2765

issn

1097-4164

pii

S1097-2765(17)30796-7

journal_volume

68

pub_type

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