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.

journal_name

Oncogene

journal_title

Oncogene

authors

Takao N,Kato H,Mori R,Morrison C,Sonada E,Sun X,Shimizu H,Yoshioka K,Takeda S,Yamamoto K

doi

10.1038/sj.onc.1203172

subject

Has Abstract

pub_date

1999-11-25 00:00:00

pages

7002-9

issue

50

eissn

0950-9232

issn

1476-5594

journal_volume

18

pub_type

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