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Title: Lyn tyrosine kinase promotes silencing of ATM-dependent checkpoint signaling during recovery from DNA double-strand breaks

Abstract

Highlights: • Inhibition of Src family kinases decreased γ-H2AX signal. • Inhibition of Src family increased ATM-dependent phosphorylation of Chk2 and Kap1. • shRNA-mediated knockdown of Lyn increased phosphorylation of Kap1 by ATM. • Ectopic expression of Src family kinase suppressed ATM-mediated Kap1 phosphorylation. • Src is involved in upstream signaling for inactivation of ATM signaling. - Abstract: DNA damage activates the DNA damage checkpoint and the DNA repair machinery. After initial activation of DNA damage responses, cells recover to their original states through completion of DNA repair and termination of checkpoint signaling. Currently, little is known about the process by which cells recover from the DNA damage checkpoint, a process called checkpoint recovery. Here, we show that Src family kinases promote inactivation of ataxia telangiectasia mutated (ATM)-dependent checkpoint signaling during recovery from DNA double-strand breaks. Inhibition of Src activity increased ATM-dependent phosphorylation of Chk2 and Kap1. Src inhibition increased ATM signaling both in G2 phase and during asynchronous growth. shRNA knockdown of Lyn increased ATM signaling. Src-dependent nuclear tyrosine phosphorylation suppressed ATM-mediated Kap1 phosphorylation. These results suggest that Src family kinases are involved in upstream signaling that leads to inactivation of the ATM-dependent DNA damage checkpoint.

Authors:
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Publication Date:
OSTI Identifier:
22416749
Resource Type:
Journal Article
Journal Name:
Biochemical and Biophysical Research Communications
Additional Journal Information:
Journal Volume: 452; Journal Issue: 3; Other Information: Copyright (c) 2014 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:
60 APPLIED LIFE SCIENCES; CELL CYCLE; DNA REPAIR; INACTIVATION; INHIBITION; PHOSPHORYLATION; PHOSPHOTRANSFERASES; STRAND BREAKS; TYROSINE

Citation Formats

Fukumoto, Yasunori, Kuki, Kazumasa, Morii, Mariko, Miura, Takahito, Honda, Takuya, Ishibashi, Kenichi, Hasegawa, Hitomi, Kubota, Sho, Ide, Yudai, Yamaguchi, Noritaka, Nakayama, Yuji, and Yamaguchi, Naoto. Lyn tyrosine kinase promotes silencing of ATM-dependent checkpoint signaling during recovery from DNA double-strand breaks. United States: N. p., 2014. Web. doi:10.1016/J.BBRC.2014.08.113.
Fukumoto, Yasunori, Kuki, Kazumasa, Morii, Mariko, Miura, Takahito, Honda, Takuya, Ishibashi, Kenichi, Hasegawa, Hitomi, Kubota, Sho, Ide, Yudai, Yamaguchi, Noritaka, Nakayama, Yuji, & Yamaguchi, Naoto. Lyn tyrosine kinase promotes silencing of ATM-dependent checkpoint signaling during recovery from DNA double-strand breaks. United States. https://doi.org/10.1016/J.BBRC.2014.08.113
Fukumoto, Yasunori, Kuki, Kazumasa, Morii, Mariko, Miura, Takahito, Honda, Takuya, Ishibashi, Kenichi, Hasegawa, Hitomi, Kubota, Sho, Ide, Yudai, Yamaguchi, Noritaka, Nakayama, Yuji, and Yamaguchi, Naoto. Fri . "Lyn tyrosine kinase promotes silencing of ATM-dependent checkpoint signaling during recovery from DNA double-strand breaks". United States. https://doi.org/10.1016/J.BBRC.2014.08.113.
@article{osti_22416749,
title = {Lyn tyrosine kinase promotes silencing of ATM-dependent checkpoint signaling during recovery from DNA double-strand breaks},
author = {Fukumoto, Yasunori and Kuki, Kazumasa and Morii, Mariko and Miura, Takahito and Honda, Takuya and Ishibashi, Kenichi and Hasegawa, Hitomi and Kubota, Sho and Ide, Yudai and Yamaguchi, Noritaka and Nakayama, Yuji and Yamaguchi, Naoto},
abstractNote = {Highlights: • Inhibition of Src family kinases decreased γ-H2AX signal. • Inhibition of Src family increased ATM-dependent phosphorylation of Chk2 and Kap1. • shRNA-mediated knockdown of Lyn increased phosphorylation of Kap1 by ATM. • Ectopic expression of Src family kinase suppressed ATM-mediated Kap1 phosphorylation. • Src is involved in upstream signaling for inactivation of ATM signaling. - Abstract: DNA damage activates the DNA damage checkpoint and the DNA repair machinery. After initial activation of DNA damage responses, cells recover to their original states through completion of DNA repair and termination of checkpoint signaling. Currently, little is known about the process by which cells recover from the DNA damage checkpoint, a process called checkpoint recovery. Here, we show that Src family kinases promote inactivation of ataxia telangiectasia mutated (ATM)-dependent checkpoint signaling during recovery from DNA double-strand breaks. Inhibition of Src activity increased ATM-dependent phosphorylation of Chk2 and Kap1. Src inhibition increased ATM signaling both in G2 phase and during asynchronous growth. shRNA knockdown of Lyn increased ATM signaling. Src-dependent nuclear tyrosine phosphorylation suppressed ATM-mediated Kap1 phosphorylation. These results suggest that Src family kinases are involved in upstream signaling that leads to inactivation of the ATM-dependent DNA damage checkpoint.},
doi = {10.1016/J.BBRC.2014.08.113},
url = {https://www.osti.gov/biblio/22416749}, journal = {Biochemical and Biophysical Research Communications},
issn = {0006-291X},
number = 3,
volume = 452,
place = {United States},
year = {2014},
month = {9}
}