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 Citations (Scopus)

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

Fingerprint

Double-Stranded DNA Breaks
gene expression
Oligonucleotide Array Sequence Analysis
genes
strands
deoxyribonucleic acid
Gene Expression
mutants
DNA
Genes
DNA repair
cells
DNA Repair
proteins
DNA-Binding Proteins
transcription (genetics)
DNA-Activated Protein Kinase
oncogenes
DNA topoisomerase
proto-oncogenes

Keywords

  • DNA repair
  • Ku80
  • Microarray
  • XRS-5

ASJC Scopus subject areas

  • Agricultural and Biological Sciences (miscellaneous)
  • Radiology Nuclear Medicine and imaging
  • Radiation
  • Radiological and Ultrasound Technology

Cite this

Differential gene expression in a DNA double-strand-break repair mutant XRS-5 defective in Ku80 : Analysis by cDNA microarray. / Chan, John Y H; Chen, Lung Kun; Chang, Jui Feng; Ting, Hui Min; Goy, Christine; Chen, Jui Lin; Hwang, Jeng Jong; Chen, Fu Du; Chen, David J.; Ngo, Frank Q H.

In: Journal of Radiation Research, Vol. 42, No. 4, 12.2001, p. 371-385.

Research output: Contribution to journalArticle

Chan, JYH, Chen, LK, Chang, JF, Ting, HM, Goy, C, Chen, JL, Hwang, JJ, Chen, FD, Chen, DJ & Ngo, FQH 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, vol. 42, no. 4, pp. 371-385. https://doi.org/10.1269/jrr.42.371
Chan, John Y H ; Chen, Lung Kun ; Chang, Jui Feng ; Ting, Hui Min ; Goy, Christine ; Chen, Jui Lin ; Hwang, Jeng Jong ; Chen, Fu Du ; Chen, David J. ; Ngo, Frank Q H. / Differential gene expression in a DNA double-strand-break repair mutant XRS-5 defective in Ku80 : Analysis by cDNA microarray. In: Journal of Radiation Research. 2001 ; Vol. 42, No. 4. pp. 371-385.
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