ATM regulates 3-methylpurine-DNA glycosylase and promotes therapeutic resistance to alkylating agents.

ABSTRACT:

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Alkylating agents are a first-line therapy for the treatment of several aggressive cancers, including pediatric glioblastoma, a lethal tumor in children. Unfortunately, many tumors are resistant to this therapy. We sought to identify ways of sensitizing tumor cells to alkylating agents while leaving normal cells unharmed, increasing therapeutic response while minimizing toxicity. Using an siRNA screen targeting over 240 DNA damage response genes, we identified novel sensitizers to alkylating agents. In particular, the base excision repair (BER) pathway, including 3-methylpurine-DNA glycosylase (MPG), as well as ataxia telangiectasia mutated (ATM), were identified in our screen. Interestingly, we identified MPG as a direct novel substrate of ATM. ATM-mediated phosphorylat

SUBMITTER: Agnihotri S 

PROVIDER: S-EPMC4184920 | biostudies-literature | 2014 Oct

REPOSITORIES: biostudies-literature