Mode of ATM-dependent suppression of chromosome translocation
Abstract
Highlights: Black-Right-Pointing-Pointer We addressed how ATM suppresses frequency of chromosome translocation. Black-Right-Pointing-Pointer We found ATM/p53-dependent G1 checkpoint suppresses translocation frequency. Black-Right-Pointing-Pointer We found ATM and DNA-PKcs function in a common pathway to suppress translocation. -- Abstract: It is well documented that deficiency in ataxia telangiectasia mutated (ATM) protein leads to elevated frequency of chromosome translocation, however, it remains poorly understood how ATM suppresses translocation frequency. In the present study, we addressed the mechanism of ATM-dependent suppression of translocation frequency. To know frequency of translocation events in a whole genome at once, we performed centromere/telomere FISH and scored dicentric chromosomes, because dicentric and translocation occur with equal frequency and by identical mechanism. By centromere/telomere FISH analysis, we confirmed that chemical inhibition or RNAi-mediated knockdown of ATM causes 2 to 2.5-fold increase in dicentric frequency at first mitosis after 2 Gy of gamma-irradiation in G0/G1. The FISH analysis revealed that ATM/p53-dependent G1 checkpoint suppresses dicentric frequency, since RNAi-mediated knockdown of p53 elevated dicentric frequency by 1.5-fold. We found ATM also suppresses dicentric occurrence independently of its checkpoint role, as ATM inhibitor showed additional effect on dicentric frequency in the context of p53 depletion and Chk1/2 inactivation. Epistasis analysis using chemical inhibitors revealedmore »
- Authors:
-
- Graduate School of Biomedical Sciences, Nagasaki University, 1-12-4 Sakamoto, Nagasaki 852-8523 (Japan)
- Publication Date:
- OSTI Identifier:
- 22207595
- Resource Type:
- Journal Article
- Journal Name:
- Biochemical and Biophysical Research Communications
- Additional Journal Information:
- Journal Volume: 416; Journal Issue: 1-2; Other Information: Copyright (c) 2011 Elsevier Science B.V., Amsterdam, The Netherlands, All rights reserved.; Country of input: International Atomic Energy Agency (IAEA); Journal ID: ISSN 0006-291X
- Country of Publication:
- United States
- Language:
- English
- Subject:
- 63 RADIATION, THERMAL, AND OTHER ENVIRONMENTAL POLLUTANT EFFECTS ON LIVING ORGANISMS AND BIOLOGICAL MATERIALS; BIOLOGICAL RADIATION EFFECTS; BUDR; CENTROMERES; DICENTRIC CHROMOSOMES; DNA; FLUORESCENCE; GAMMA RADIATION; INHIBITION; IN-SITU HYBRIDIZATION; MITOSIS; PROTEINS; STRAND BREAKS; TRANSLOCATION
Citation Formats
Yamauchi, Motohiro, Suzuki, Keiji, Oka, Yasuyoshi, Suzuki, Masatoshi, Kondo, Hisayoshi, and Yamashita, Shunichi. Mode of ATM-dependent suppression of chromosome translocation. United States: N. p., 2011.
Web. doi:10.1016/J.BBRC.2011.11.006.
Yamauchi, Motohiro, Suzuki, Keiji, Oka, Yasuyoshi, Suzuki, Masatoshi, Kondo, Hisayoshi, & Yamashita, Shunichi. Mode of ATM-dependent suppression of chromosome translocation. United States. https://doi.org/10.1016/J.BBRC.2011.11.006
Yamauchi, Motohiro, Suzuki, Keiji, Oka, Yasuyoshi, Suzuki, Masatoshi, Kondo, Hisayoshi, and Yamashita, Shunichi. 2011.
"Mode of ATM-dependent suppression of chromosome translocation". United States. https://doi.org/10.1016/J.BBRC.2011.11.006.
@article{osti_22207595,
title = {Mode of ATM-dependent suppression of chromosome translocation},
author = {Yamauchi, Motohiro and Suzuki, Keiji and Oka, Yasuyoshi and Suzuki, Masatoshi and Kondo, Hisayoshi and Yamashita, Shunichi},
abstractNote = {Highlights: Black-Right-Pointing-Pointer We addressed how ATM suppresses frequency of chromosome translocation. Black-Right-Pointing-Pointer We found ATM/p53-dependent G1 checkpoint suppresses translocation frequency. Black-Right-Pointing-Pointer We found ATM and DNA-PKcs function in a common pathway to suppress translocation. -- Abstract: It is well documented that deficiency in ataxia telangiectasia mutated (ATM) protein leads to elevated frequency of chromosome translocation, however, it remains poorly understood how ATM suppresses translocation frequency. In the present study, we addressed the mechanism of ATM-dependent suppression of translocation frequency. To know frequency of translocation events in a whole genome at once, we performed centromere/telomere FISH and scored dicentric chromosomes, because dicentric and translocation occur with equal frequency and by identical mechanism. By centromere/telomere FISH analysis, we confirmed that chemical inhibition or RNAi-mediated knockdown of ATM causes 2 to 2.5-fold increase in dicentric frequency at first mitosis after 2 Gy of gamma-irradiation in G0/G1. The FISH analysis revealed that ATM/p53-dependent G1 checkpoint suppresses dicentric frequency, since RNAi-mediated knockdown of p53 elevated dicentric frequency by 1.5-fold. We found ATM also suppresses dicentric occurrence independently of its checkpoint role, as ATM inhibitor showed additional effect on dicentric frequency in the context of p53 depletion and Chk1/2 inactivation. Epistasis analysis using chemical inhibitors revealed that ATM kinase functions in the same pathway that requires kinase activity of DNA-dependent protein kinase catalytic subunit (DNA-PKcs) to suppress dicentric frequency. From the results in the present study, we conclude that ATM minimizes translocation frequency through its commitment to G1 checkpoint and DNA double-strand break repair pathway that requires kinase activity of DNA-PKcs.},
doi = {10.1016/J.BBRC.2011.11.006},
url = {https://www.osti.gov/biblio/22207595},
journal = {Biochemical and Biophysical Research Communications},
issn = {0006-291X},
number = 1-2,
volume = 416,
place = {United States},
year = {Fri Dec 09 00:00:00 EST 2011},
month = {Fri Dec 09 00:00:00 EST 2011}
}