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


METHODS
U937 cells were treated with gamma-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.


CONCLUSIONS
ATM belongs to a group of repair proteins, including PARP, DNA-PK and HsRad51, which are specifically cleaved during apoptosis. These findings support the idea that repair mechanisms need to be inactivated for apoptosis to proceed efficiently.
Tong
X
X
Beijing Institute of Radiation Medicine, PR China.
Liu
B
B
Dong
Y
Y
Sun
Z
Z
D017209:Apoptosis / Q000528:radiation effects*; D064007:Ataxia Telangiectasia Mutated Proteins; D053148:Caspase 3; D020169:Caspases / Q000502:physiology*; D018797:Cell Cycle Proteins; D004249:DNA Damage; D004260:DNA Repair; D004268:DNA-Binding Proteins; D018922:HL-60 Cells; D006801:Humans; D011065:Poly(ADP-ribose) Polymerases / Q000502:physiology; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism*; D025521:Tumor Suppressor Proteins; D020298:U937 Cells
D018797:Cell Cycle Proteins; D004268:DNA-Binding Proteins; D025521:Tumor Suppressor Proteins; D011065:Poly(ADP-ribose) Polymerases; C576324:ATM protein, human; D064007:Ataxia Telangiectasia Mutated Proteins; D017346:Protein Serine-Threonine Kinases; C505407:CASP3 protein, human; D053148:Caspase 3; D020169:Caspases