Disruption of the BLM gene in ATM-null DT40 cells does not exacerbate either phenotype.
Bloom syndrome and ataxia-telangiectasia are autosomal recessive human disorders characterized by immunodeficiency, genome instability and predisposition to develop cancer. Recent data reveal that the products of these two genes, BLM and ATM, interact and function together in recognizing abnormal DNA structures. To investigate the function of these two molecules in DNA damage recognition, we generated double knockouts of ATM(-/-) BLM(-/-) in the DT40 chicken B-lymphocyte cell line. The double mutant cells were viable and exhibited a variety of characteristics of both ATM(-/-) and BLM(-/-) cells. There was no evidence for exacerbation of either phenotype; however, the more extreme radiosensitivity seen in ATM(-/-) and the elevated sister chromatid exchange seen in BLM(-/-) cells were retained in the double mutants. These results suggest that ATM and BLM have largely distinct roles in recognizing different forms of damage in DNA, but are also compatible with partially overlapping functions in recognizing breaks in radiation-damaged DNA.
Department of Pediatrics, Gifu University School of Medicine, Gifu 500-8076, Japan.
Toshiyuki
T
Fukao
Philip
P
Chen
Jun
J
Ren
Hideo
H
Kaneko
Gai Xiu
GX
Zhang
Masahi
M
Kondo
Ken-Ichi
K
Yamamoto
Yasuhiro
Y
Furuichi
Shunichi
S
Takeda
Naomi
N
Kondo
Martin F
MF
Lavin
D000251:Adenosine Triphosphatases / Q000235:genetics*; D000818:Animals; D001260:Ataxia Telangiectasia / Q000235:genetics*; D001402:B-Lymphocytes; D002455:Cell Division / Q000187:drug effects / Q000528:radiation effects; D002645:Chickens; D002869:Chromosome Aberrations / Q000528:radiation effects; D002999:Clone Cells; D004247:DNA / Q000528:radiation effects; D004249:DNA Damage; D004265:DNA Helicases / Q000235:genetics*; D008954:Models, Biological; D009154:Mutation; D010641:Phenotype; D053484:RecQ Helicases
D004247:DNA; D000251:Adenosine Triphosphatases; C097151:Bloom syndrome protein; D004265:DNA Helicases; D053484:RecQ Helicases