ATM mediates repression of DNA end-degradation in an ATP-dependent manner.

DNA Repair
Elias A RahalK Dixon

Abstract

Ataxia telangiectasia mutated (ATM) is a PI3-kinase-like kinase (PIKK) associated with DNA double-strand break (DSB) repair and cell cycle control. We have previously reported comparable efficiencies of DSB repair in nuclear extracts from both ATM deficient (A-T) and control (ATM+) cells; however, the repair products from the A-T nuclear extracts contained deletions encompassing longer stretches of DNA compared to controls. These deletions appeared to result from end-joining at sites of microhomology. These data suggest that ATM hinders error-prone repair pathways that depend on degradation of DNA ends at a break. Such degradation may account for the longer deletions we formerly observed in A-T cell extracts. To address this possibility we assessed the degradation of DNA duplex substrates in A-T and control nuclear extracts under DSB repair conditions. We observed a marked shift in signal intensity from full-length products to shorter products in A-T nuclear extracts, and addition of purified ATM to A-T nuclear extracts restored full-length product detection. This repression of degradation by ATM was both ATP-dependent and inhibited by the PIKK inhibitors wortmannin and caffeine. Addition of pre-phosphorylated ATM to an A-T nuc...Continue Reading

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Citations

Feb 28, 2014·Nature Communications·Alejandro Álvarez-QuilónFelipe Cortés-Ledesma
Sep 14, 2011·Annual Review of Genetics·Lorraine S Symington, Jean Gautier
Sep 12, 2015·Critical Reviews in Oncology/hematology·Loredana UrsoGiulia Pasello
Jan 31, 2009·Journal of Cellular Biochemistry·Lin NiYoshinori Kamisaki
Jan 31, 2020·Frontiers in Molecular Biosciences·Almudena Serrano-BenítezJose F Ruiz
Feb 27, 2009·Cancer Research·Alyssa Bouska, Christine M Eischen

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