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 Celljournal_title
Molecular cellauthors
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 JIdoi
10.1016/j.molcel.2017.10.021subject
Has Abstractpub_date
2017-11-16 00:00:00pages
797-807.e7issue
4eissn
1097-2765issn
1097-4164pii
S1097-2765(17)30796-7journal_volume
68pub_type
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