CHK1 affecting cell radiosensitivity is independent of non-homologous end joining.
CHK1 is one of the most important checkpoint proteins in mammalian cells for responding to DNA damage. Cells defective in CHK1 are sensitive to ionizing radiation (IR). The mechanism by which CHK1 protects cells from IR-induced killing remains unclear. DNA double strand breaks (DSBs) induced by IR are critical lesions for cell survival. Two major complementary DNA DSBs repair pathways exist in mammalian cells, homologous recombination repair (HRR) and nonhomologous end joining (NHEJ). By using CHK1 kinase dead human cell lines established in our laboratory, we show here that although these human cell lines have different CHK1 activities with different sensitivities to IR-induced killing and G(2) accumulation, all these cell lines show similar inductions and rejoining rates of DNA DSBs. These results indicate that the different radiosensitivities and G(2) checkpoint responses in these cell lines are independent of NHEJ, suggesting that CHK1-regulated checkpoint facilitates HRR and therefore protects cells from IR-induced killing.
Wang
Hongyan
H
Department of Radiation Oncology, Kimmel Cancer Center of Jefferson Medical College, Thomas Jefferson University, Philadelphia, Pennsylvania 19107, USA.
Hu
Baocheng
B
Liu
Ronghua
R
Wang
Ya
Y
D016923:Cell Death; D002460:Cell Line; D000071877:Checkpoint Kinase 1; D019457:Chromosome Breakage; D004247:DNA / Q000235:genetics / Q000378:metabolism / Q000528:radiation effects; D004249:DNA Damage; D004260:DNA Repair / Q000235:genetics / Q000502:physiology / Q000528:radiation effects; D016195:G2 Phase; D006801:Humans; D018499:Linear Energy Transfer; D011494:Protein Kinases / Q000235:genetics / Q000502:physiology*; D011839:Radiation, Ionizing; D011995:Recombination, Genetic; D012689:Sequence Homology, Nucleic Acid; D014162:Transfection
D004247:DNA; D011494:Protein Kinases; C000605867:CHEK1 protein, human; D000071877:Checkpoint Kinase 1