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Int. J. Mol. Sci. 2016, 17(6), 871; doi:10.3390/ijms17060871

v-Src Causes Chromosome Bridges in a Caffeine-Sensitive Manner by Generating DNA Damage

1
Department of Biochemistry & Molecular Biology, Kyoto Pharmaceutical University, Kyoto 607-8414, Japan
2
Department of Molecular Cell Biology, Graduate School of Pharmaceutical Sciences, Chiba University, Chiba 260-8675, Japan
*
Author to whom correspondence should be addressed.
Academic Editor: Guillermo T. Sáez
Received: 28 March 2016 / Revised: 25 May 2016 / Accepted: 27 May 2016 / Published: 2 June 2016
(This article belongs to the Special Issue DNA Damage and Repair in Degenerative Diseases 2016)
View Full-Text   |   Download PDF [4300 KB, uploaded 2 June 2016]   |  

Abstract

An increase in Src activity is commonly observed in epithelial cancers. Aberrant activation of the kinase activity is associated with malignant progression. However, the mechanisms that underlie the Src-induced malignant progression of cancer are not completely understood. We show here that v-Src, an oncogene that was first identified from a Rous sarcoma virus and a mutant variant of c-Src, leads to an increase in the number of anaphase and telophase cells having chromosome bridges. v-Src increases the number of γH2AX foci, and this increase is inhibited by treatment with PP2, a Src kinase inhibitor. v-Src induces the phosphorylation of KAP1 at Ser824, Chk2 at Thr68, and Chk1 at Ser345, suggesting the activation of the ATM/ATR pathway. Caffeine decreases the number of cells having chromosome bridges at a concentration incapable of inhibiting Chk1 phosphorylation at Ser345. These results suggest that v-Src induces chromosome bridges via generation of DNA damage and the subsequent DNA damage response, possibly by homologous recombination. A chromosome bridge gives rise to the accumulation of DNA damage directly through chromosome breakage and indirectly through cytokinesis failure-induced multinucleation. We propose that v-Src-induced chromosome bridge formation is one of the causes of the v-Src-induced malignant progression of cancer cells. View Full-Text
Keywords: v-Src; chromosome bridge; DNA damage; caffeine v-Src; chromosome bridge; DNA damage; caffeine
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Ikeuchi, M.; Fukumoto, Y.; Honda, T.; Kuga, T.; Saito, Y.; Yamaguchi, N.; Nakayama, Y. v-Src Causes Chromosome Bridges in a Caffeine-Sensitive Manner by Generating DNA Damage. Int. J. Mol. Sci. 2016, 17, 871.

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