Differential gene expression in a DNA double-strand-break repair mutant XRS-5 defective in Ku80: Analysis by cDNA microarray

John Y H Chan, Lung Kun Chen, Jui Feng Chang, Hui Min Ting, Christine Goy, Jui Lin Chen, Jeng Jong Hwang, Fu Du Chen, David J. Chen, Frank Q H Ngo

Research output: Contribution to journalArticle

10 Scopus citations

Abstract

The ability of cells to rejoin DNA double-strand breaks (DSBs) usually correlates with their radiosensitivity. This correlation has been demonstrated in radiosensitive cells, including the Chinese hamster ovary mutant XRS-5. XRS-5 is detective in a DNA end-binding protein. Ku80. which is a component of a DNA-dependent protein kinase complex used for joining strand breaks. However, Ku80-deficient cells are known to be retarded in cell proliferation and growth as well as other yet to be identified defects. Using custom-made 600-gene cDNA microarray filters, we found differential gene expressions between the wild-type and XRS-5 cells. Defective Ku80 apparently affects the expression of several repair genes, including topoisomerase-I and -IIA, ERCC5, MLH1, and ATM. In contrast, other DNA repair-associated genes, such as GADD45A, EGR1 MDM2 and p53, were not affected. In addition, for large numbers of growth-associated genes, such as cyclins and clks, the growth factors and cytokines were also affected. Down-regulated expression was also found in several categories of seemingly unrelated genes, including apoptosis, angiogenesis, kinase and signaling, phosphatase, stress protein, proto-oncogenes and tumor suppressors, transcription and translation factors. A RT-PCR analysis confirmed that the XRS-5 cells used were defective in Ku80 expression. The diversified groups of genes being affected could mean that Ku80, a multi-functional DNA-binding protein, not only affects DNA repair, but is also involved in transcription regulation. Our data, taken together, indicate that there are specific genes being modulated in Ku80-deficient cells, and that some of the DNA repair pathways and other biological functions are apparently linked, suggesting that a defect in one gene could have global effects on many other processes.

Original languageEnglish (US)
Pages (from-to)371-385
Number of pages15
JournalJournal of radiation research
Volume42
Issue number4
DOIs
StatePublished - Dec 2001

Keywords

  • DNA repair
  • Ku80
  • Microarray
  • XRS-5

ASJC Scopus subject areas

  • Radiation
  • Radiology Nuclear Medicine and imaging
  • Health, Toxicology and Mutagenesis

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    Chan, J. Y. H., Chen, L. K., Chang, J. F., Ting, H. M., Goy, C., Chen, J. L., Hwang, J. J., Chen, F. D., Chen, D. J., & Ngo, F. Q. H. (2001). Differential gene expression in a DNA double-strand-break repair mutant XRS-5 defective in Ku80: Analysis by cDNA microarray. Journal of radiation research, 42(4), 371-385. https://doi.org/10.1269/jrr.42.371