Disruption of ATM in p53-null cells causes multiple functional abnormalities in cellular response to ionizing radiation

Noriaki Takao; Hideaki Kato; Ryoichi Mori; Ciaran Morrison; Eiichiro Sonada; Xiango Sun; Hiroko Shimizu; Katsuji Yoshioka; Shunichi Takeda; Ken Ichi Yamamoto

doi:10.1038/sj.onc.1203172

Disruption of ATM in p53-null cells causes multiple functional abnormalities in cellular response to ionizing radiation

Noriaki Takao, Hideaki Kato, Ryoichi Mori, Ciaran Morrison, Eiichiro Sonada, Xiango Sun, Hiroko Shimizu, Katsuji Yoshioka, Shunichi Takeda, Ken Ichi Yamamoto

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

92 Citations (Scopus)

Abstract

ATM is a member of the large phosphatidylinositol-3 kinase family and plays an important role in cellular response to DNA damage. To further define the physiological roles of ATM at the cellular level, we created an isogenic set of stable cell lines differing only in their ATM status from the chicken B cell line DT40 by targeted integration. These stable DT40 cell lines, as most of transformed chicken cell lines, do not express p53. However, ATM(-/-) DT40 cells displayed retarded cellular proliferation, defective G₂/M checkpoint control and radio-resistant DNA synthesis. Furthermore, ATM(-/-) DT40 cells were sensitive to ionizing radiation and showed highly elevated frequencies of both spontaneous and radiation-induced chromosomal aberrations. In addition, a slight but significant reduction in targeted integration frequency was observed in ATM(-/-) DT40 cells. These results suggest that ATM has multiple p53-independent functions in cell cycle checkpoint control and in maintenance of chromosomal DNA. These ATM deficient DT40 clones therefore provide a useful model system for analysing p53-independent ATM functions.

Original language	English
Pages (from-to)	7002-7009
Number of pages	8
Journal	Oncogene
Volume	18
Issue number	50
DOIs	https://doi.org/10.1038/sj.onc.1203172
Publication status	Published - Nov 25 1999
Externally published	Yes

Keywords

ATM disruption
Cell cycle checkpoint
DNA repair
p53

ASJC Scopus subject areas

Molecular Biology
Genetics
Cancer Research

UN SDGs

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

Access to Document

10.1038/sj.onc.1203172

Cite this

@article{730a6c783f5140e9a9c062fc8b59db62,

title = "Disruption of ATM in p53-null cells causes multiple functional abnormalities in cellular response to ionizing radiation",

abstract = "ATM is a member of the large phosphatidylinositol-3 kinase family and plays an important role in cellular response to DNA damage. To further define the physiological roles of ATM at the cellular level, we created an isogenic set of stable cell lines differing only in their ATM status from the chicken B cell line DT40 by targeted integration. These stable DT40 cell lines, as most of transformed chicken cell lines, do not express p53. However, ATM(-/-) DT40 cells displayed retarded cellular proliferation, defective G2/M checkpoint control and radio-resistant DNA synthesis. Furthermore, ATM(-/-) DT40 cells were sensitive to ionizing radiation and showed highly elevated frequencies of both spontaneous and radiation-induced chromosomal aberrations. In addition, a slight but significant reduction in targeted integration frequency was observed in ATM(-/-) DT40 cells. These results suggest that ATM has multiple p53-independent functions in cell cycle checkpoint control and in maintenance of chromosomal DNA. These ATM deficient DT40 clones therefore provide a useful model system for analysing p53-independent ATM functions.",

keywords = "ATM disruption, Cell cycle checkpoint, DNA repair, p53",

author = "Noriaki Takao and Hideaki Kato and Ryoichi Mori and Ciaran Morrison and Eiichiro Sonada and Xiango Sun and Hiroko Shimizu and Katsuji Yoshioka and Shunichi Takeda and Yamamoto, {Ken Ichi}",

note = "Funding Information: We would like to acknowledge K Horiguchi and Y Sato for excellent technical assistance. C Morrison is the recipient of a JSPS Postdoctoral fellowship. This work is supported in part by Grants-in-Aid from the Ministry of Education, Science and Culture of Japan.",

year = "1999",

month = nov,

day = "25",

doi = "10.1038/sj.onc.1203172",

language = "English",

volume = "18",

pages = "7002--7009",

journal = "Oncogene",

issn = "0950-9232",

publisher = "Nature Publishing Group",

number = "50",

}

TY - JOUR

T1 - Disruption of ATM in p53-null cells causes multiple functional abnormalities in cellular response to ionizing radiation

AU - Takao, Noriaki

AU - Kato, Hideaki

AU - Mori, Ryoichi

AU - Morrison, Ciaran

AU - Sonada, Eiichiro

AU - Sun, Xiango

AU - Shimizu, Hiroko

AU - Yoshioka, Katsuji

AU - Takeda, Shunichi

AU - Yamamoto, Ken Ichi

N1 - Funding Information: We would like to acknowledge K Horiguchi and Y Sato for excellent technical assistance. C Morrison is the recipient of a JSPS Postdoctoral fellowship. This work is supported in part by Grants-in-Aid from the Ministry of Education, Science and Culture of Japan.

PY - 1999/11/25

Y1 - 1999/11/25

N2 - ATM is a member of the large phosphatidylinositol-3 kinase family and plays an important role in cellular response to DNA damage. To further define the physiological roles of ATM at the cellular level, we created an isogenic set of stable cell lines differing only in their ATM status from the chicken B cell line DT40 by targeted integration. These stable DT40 cell lines, as most of transformed chicken cell lines, do not express p53. However, ATM(-/-) DT40 cells displayed retarded cellular proliferation, defective G2/M checkpoint control and radio-resistant DNA synthesis. Furthermore, ATM(-/-) DT40 cells were sensitive to ionizing radiation and showed highly elevated frequencies of both spontaneous and radiation-induced chromosomal aberrations. In addition, a slight but significant reduction in targeted integration frequency was observed in ATM(-/-) DT40 cells. These results suggest that ATM has multiple p53-independent functions in cell cycle checkpoint control and in maintenance of chromosomal DNA. These ATM deficient DT40 clones therefore provide a useful model system for analysing p53-independent ATM functions.

AB - ATM is a member of the large phosphatidylinositol-3 kinase family and plays an important role in cellular response to DNA damage. To further define the physiological roles of ATM at the cellular level, we created an isogenic set of stable cell lines differing only in their ATM status from the chicken B cell line DT40 by targeted integration. These stable DT40 cell lines, as most of transformed chicken cell lines, do not express p53. However, ATM(-/-) DT40 cells displayed retarded cellular proliferation, defective G2/M checkpoint control and radio-resistant DNA synthesis. Furthermore, ATM(-/-) DT40 cells were sensitive to ionizing radiation and showed highly elevated frequencies of both spontaneous and radiation-induced chromosomal aberrations. In addition, a slight but significant reduction in targeted integration frequency was observed in ATM(-/-) DT40 cells. These results suggest that ATM has multiple p53-independent functions in cell cycle checkpoint control and in maintenance of chromosomal DNA. These ATM deficient DT40 clones therefore provide a useful model system for analysing p53-independent ATM functions.

KW - ATM disruption

KW - Cell cycle checkpoint

KW - DNA repair

KW - p53

UR - http://www.scopus.com/inward/record.url?scp=0033604444&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0033604444&partnerID=8YFLogxK

U2 - 10.1038/sj.onc.1203172

DO - 10.1038/sj.onc.1203172

M3 - Article

C2 - 10597300

AN - SCOPUS:0033604444

SN - 0950-9232

VL - 18

SP - 7002

EP - 7009

JO - Oncogene

JF - Oncogene

IS - 50

ER -

Disruption of ATM in p53-null cells causes multiple functional abnormalities in cellular response to ionizing radiation

Abstract

Keywords

ASJC Scopus subject areas

UN SDGs

Access to Document

Other files and links

Fingerprint

Cite this