Disruption of the BLM gene in ATM-null DT40 cells does not exacerbate either phenotype

Toshiyuki Fukao; Philip Chen; Jun Ren; Hideo Kaneko; Gai Xiu Zhang; Masahi Kondo; Ken Ichi Yamamoto; Yasuhiro Furuichi; Shunichi Takeda; Naomi Kondo; Martin F. Lavin

doi:10.1038/sj.onc.1207276

Disruption of the BLM gene in ATM-null DT40 cells does not exacerbate either phenotype

Toshiyuki Fukao, Philip Chen, Jun Ren, Hideo Kaneko, Gai Xiu Zhang, Masahi Kondo, Ken Ichi Yamamoto, Yasuhiro Furuichi, Shunichi Takeda, Naomi Kondo, Martin F. Lavin

Research output: Contribution to journal › Article › peer-review

5 Citations (Scopus)

Abstract

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.

Original language	English
Pages (from-to)	1498-1506
Number of pages	9
Journal	Oncogene
Volume	23
Issue number	8
DOIs	https://doi.org/10.1038/sj.onc.1207276
Publication status	Published - Feb 26 2004
Externally published	Yes

Keywords

Ataxia-telangiectasia
Bloom syndrome
DNA damage
DT40 cells
Gene disruption

ASJC Scopus subject areas

Molecular Biology
Genetics
Cancer Research

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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10.1038/sj.onc.1207276

Cite this

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title = "Disruption of the BLM gene in ATM-null DT40 cells does not exacerbate either phenotype",

abstract = "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.",

keywords = "Ataxia-telangiectasia, Bloom syndrome, DNA damage, DT40 cells, Gene disruption",

author = "Toshiyuki Fukao and Philip Chen and Jun Ren and Hideo Kaneko and Zhang, {Gai Xiu} and Masahi Kondo and Yamamoto, {Ken Ichi} and Yasuhiro Furuichi and Shunichi Takeda and Naomi Kondo and Lavin, {Martin F.}",

note = "Funding Information: We thank Aine Farrell for technical support and Tracey Laing for typing this manuscript. Support was provided by the Australian National Health and Medical Research Council, the A-T Children{\textquoteright}s Foundation, the National Institutes of Health USA, the Australia–Japan Co-operative Research Program and the Uehara Research Foundation.",

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doi = "10.1038/sj.onc.1207276",

language = "English",

volume = "23",

pages = "1498--1506",

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T1 - Disruption of the BLM gene in ATM-null DT40 cells does not exacerbate either phenotype

AU - Fukao, Toshiyuki

AU - Chen, Philip

AU - Ren, Jun

AU - Kaneko, Hideo

AU - Zhang, Gai Xiu

AU - Kondo, Masahi

AU - Yamamoto, Ken Ichi

AU - Furuichi, Yasuhiro

AU - Takeda, Shunichi

AU - Kondo, Naomi

AU - Lavin, Martin F.

N1 - Funding Information: We thank Aine Farrell for technical support and Tracey Laing for typing this manuscript. Support was provided by the Australian National Health and Medical Research Council, the A-T Children’s Foundation, the National Institutes of Health USA, the Australia–Japan Co-operative Research Program and the Uehara Research Foundation.

PY - 2004/2/26

Y1 - 2004/2/26

N2 - 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.

AB - 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.

KW - Ataxia-telangiectasia

KW - Bloom syndrome

KW - DNA damage

KW - DT40 cells

KW - Gene disruption

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Disruption of the BLM gene in ATM-null DT40 cells does not exacerbate either phenotype

Abstract

Keywords

ASJC Scopus subject areas

UN SDGs

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