Cleavage of ATM during radiation-induced apoptosis: Caspase-3-like apoptotic protease as a candidate

X. Tong, B. Liu, Y. Dong, Z. Sun*

*Corresponding author for this work

Research output: Contribution to journalArticle

20 Scopus citations

Abstract

Purpose: To study the relationship of ionizing radiation-induced apoptosis with the integrity of ATM (mutated in ataxia telangiectasia) that has a critical role in DNA damage sensing and repair, cell-cycle checkpoint controls and maintenance of genomic stability. Materials and methods: U937 cells were treated with γ-radiation. Sub-G1 DNA content, DNA fragmentation, cleavage of PARP, active caspase-3, cleavage of ATM in vivo and in vitro were measured by flow cytometry, agarose gel electrophoresis, cleaving of colorimetric caspase-3 substrate and Western blotting. Results: ATM is specifically cleaved in cells during the induction of apoptosis by ionizing radiation exposure. The time-course of cleavage coincided with the appearance of cells with a sub-G1 DNA content and activation of caspase-3. ATM was cleaved with similar kinetics as PARP and DEVD-FMK could abolish the cleavage. In vitro studies showed that ATM was cleaved by caspase-3 or related subfamily members at a DIVD/G site. Conclusion: ATM belongs to a group of repair proteins, including PARP, DNA-PK and HsRad5I, which are specifically cleaved during apoptosis. These findings support the idea that repair mechanisms need to be inactivated for apoptosis to proceed efficiently.

Original languageEnglish (US)
Pages (from-to)1387-1395
Number of pages9
JournalInternational Journal of Radiation Biology
Volume76
Issue number10
StatePublished - 2000

ASJC Scopus subject areas

  • Radiological and Ultrasound Technology
  • Radiology Nuclear Medicine and imaging

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