Drosophila Chk2 is required for DNA damage-mediated cell cycle arrest and apoptosis.
Chk2 is a major target of ataxia telangiectasia-mutated (ATM) and ATM- and Rad3-related (ATR). Germline mutations in Chk2 have been identified in a subset of patients with Li-Fraumeni syndrome, suggesting that Chk2 is a tumor suppressor gene. To investigate the role of Chk2 in multicellular organisms, a Drosophila chk2 (Dmchk2) mutant was generated. Dmchk2 mutants are viable but show defects in maintaining genome stability and are highly sensitive to ionizing radiation. Interestingly, mutating Dmchk2 completely blocks DNA damage-induced apoptosis and partially blocks DNA damage-induced cell cycle arrest. These results indicate that Chk2 protein plays a crucial role in the DNA damage response pathway mediating cell cycle arrest and apoptosis, and that the ATM-Chk2 pathway is likely conserved in Drosophila.
Xu
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Ben May Institute for Cancer Research and Center for Molecular Oncology, University of Chicago, 924 E. 57th Street, Chicago, IL 60637, USA.
Xin
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Du
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D000818:Animals; D017209:Apoptosis; D002453:Cell Cycle; D064447:Checkpoint Kinase 2; D004249:DNA Damage; D004330:Drosophila / Q000235:genetics / Q000502:physiology* / Q000528:radiation effects; D029721:Drosophila Proteins / Q000235:genetics / Q000378:metabolism; D016254:Mutagenesis, Insertional; D017346:Protein Serine-Threonine Kinases / Q000235:genetics / Q000378:metabolism*
D029721:Drosophila Proteins; D064447:Checkpoint Kinase 2; D017346:Protein Serine-Threonine Kinases; C112435:lok protein, Drosophila