HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Full Text Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Takao, N. Articles by Yamamoto, K.-i. Search for Related Content PubMed PubMed Citation Articles by Takao, N. Articles by Yamamoto, K.-i. Social Bookmarking                      What's this?

J Biol Chem, Vol. 275, Issue 2, 725-728, January 14, 2000

ACCELERATED PUBLICATION
c-Abl Tyrosine Kinase Is Not Essential for Ataxia Telangiectasia Mutated Functions in Chromosomal Maintenance^*

Noriaki Takao, Ryoichi Mori, Hideaki Kato, Akira Shinohara^§, and Ken-ichi Yamamoto^¶

From the Department of Molecular Pathology, Cancer Research Institute and the  Department of Surgery I, Kanazawa University, Kanazawa 920-0934, Japan and the ^§ Department of Radiation and Cellular Oncology, University of Chicago, Chicago, Illinois 60637

c-Abl is activated by DNA damage in an ataxia telangiectasia mutated (ATM)-dependent manner and plays important roles in growth arrest and apoptosis induced by DNA damage. c-Abl also interacts physically and functionally with Rad51, a key molecule in homologous recombinational (HR) DNA repair. To study further the roles of c-Abl in HR DNA repair, we generated c-Abl^/ and ATM^//c-Abl^/ mutant cell lines from a chicken B lymphocyte DT40 cell line, comparing the phenotypes of these mutants to those of ATM^/ DT40 cells that we had created previously. We found that the time course of radiation-induced Rad51 focus formation is abnormal in ATM^/ DT40 cells, consistent with the observation that ATM^/ DT40 cells display hypersensitivity to ionizing radiation and highly elevated frequencies of both spontaneous and radiation-induced chromosomal aberrations. In contrast, c-Abl^/ cells did not show these ATM-related defects in their cellular response to radiation, nor did the disruption of c-Abl in ATM^/ DT40 cells exacerbate these ATM-related defects. However, c-Abl^/ DT40 cells, but not ATM^/ DT40 cells, were resistant to radiation-induced apoptosis, indicating an important role for c-Abl in this cellular response to ionizing radiation. These results therefore indicate that, although ATM plays an important role in genome maintenance, c-Abl is not essential for this ATM function. These findings suggest that c-Abl and ATM play important roles in the maintenance of the cell homeostasis in response to DNA damage that are, at least in part, independent.

---

^* This work is supported in part by grants-in-aid from the Ministry of Education, Science and Culture of Japan.The costs of publication of this article were defrayed in part by the payment of page charges. The article must therefore be hereby marked "advertisement" in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

^¶ To whom correspondence should be addressed: Dept. of Molecular Pathology, Cancer Research Institute, Kanazawa University, 13-1 Takaramachi, Kanazawa, Ishikawa 920-0934, Japan. Tel.: 81-76-265-2755; Fax: 81-76-234-4516; E-mail: kyamamot@kenroku.kanazawa-u. ac.jp.

---

Copyright © 2000 by The American Society for Biochemistry and Molecular Biology, Inc.

CiteULike

Complore

Connotea

Del.icio.us

Digg

Reddit

Technorati

This article has been cited by other articles:

				Q. L. K. Lam, C. K. C. Lo, B.-J. Zheng, K.-H. Ko, D. G. Osmond, G. E. Wu, R. Rottapel, and L. Lu Impaired V(D)J recombination and increased apoptosis among B cell precursors in the bone marrow of c-Abl-deficient mice Int. Immunol., March 1, 2007; 19(3): 267 - 276. [Abstract] [Full Text] [PDF]

				J. He, Y. Tohyama, K.-i. Yamamoto, M. Kobayashi, Y. Shi, T. Takano, C. Noda, K. Tohyama, and H. Yamamura Lysosome is a primary organelle in B cell receptor-mediated apoptosis: an indispensable role of Syk in lysosomal function Genes Cells, January 1, 2005; 10(1): 23 - 35. [Abstract] [Full Text] [PDF]

				B. Li, X. Wang, N. Rasheed, Y. Hu, S. Boast, T. Ishii, K. Nakayama, K. I. Nakayama, and S. P. Goff Distinct roles of c-Abl and Atm in oxidative stress response are mediated by protein kinase C {delta} Genes & Dev., August 1, 2004; 18(15): 1824 - 1837. [Abstract] [Full Text] [PDF]

				M. Kobayashi, A. Hirano, T. Kumano, S.-L. Xiang, K. Mihara, Y. Haseda, O. Matsui, H. Shimizu, and K.-i. Yamamoto Critical role for chicken Rad17 and Rad9 in the cellular response to DNA damage and stalled DNA replication Genes Cells, April 1, 2004; 9(4): 291 - 303. [Abstract] [Full Text] [PDF]

				J. Yang, Y. Yu, H. E. Hamrick, and P. J. Duerksen-Hughes ATM, ATR and DNA-PK: initiators of the cellular genotoxic stress responses Carcinogenesis, October 1, 2003; 24(10): 1571 - 1580. [Abstract] [Full Text] [PDF]

				J. Roig, P. T. Tuazon, P. A. Zipfel, A. M. Pendergast, and J. A. Traugh Functional interaction between c-Abl and the p21-activated protein kinase gamma -PAK PNAS, December 19, 2000; 97(26): 14346 - 14351. [Abstract] [Full Text] [PDF]

				N. Uemura and J. D. Griffin The ABL kinase inhibitor STI571 does not affect survival of hematopoietic cells after ionizing radiation Blood, November 1, 2000; 96(9): 3294 - 3295. [Full Text] [PDF]