Differential Gene Expression in a DNA Double-strand-breakRepair Mutant XRS-5 Defective in Ku80: Analysisby cDNA Microarray

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概要

• 論文の詳細を見る

• 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 defective 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.

• 日本放射線影響学会の論文

著者

• Chen David

  台湾

• Goy Christine

  Institute Of Radiological Sciences National Yang Ming University

• CHAN JOHN

  Institute of Radiological Sciences, National Yang Ming University

• CHEN LUNG-KUN

  Institute of Radiological Sciences, National Yang Ming University

• CHANG JUI-FENG

  Institute of Radiological Sciences, National Yang Ming University

• TING HUI-MIN

  Institute of Radiological Sciences, National Yang Ming University

• CHEN JUI-LIN

  Institute of Radiological Sciences, National Yang Ming University

• HWANG JENG-JONG

  Institute of Radiological Sciences, National Yang Ming University

• CHEN FU-DU

  Institute of Radiological Sciences, National Yang Ming University

• CHEN DAVID

  Division of Life Sciences, Lawrence Berkeley National laboratory

• NGO FRANK

  Institute of Radiological Sciences, National Yang Ming University

• Chan John

  Institute Of Radiological Sciences National Yang Ming University

• Ngo Frank

  Institute Of Radiological Sciences National Yang Ming University

• Chen Fu-du

  Institute Of Radiological Sciences National Yang Ming University

• Chen David

  Division Of Life Sciences Lawrence Berkeley National Laboratory

• Hwang Jeng-jong

  Institute Of Radiological Sciences National Yang Ming University

• Ting Hui-min

  Institute Of Radiological Sciences National Yang Ming University

• Chen Lung-kun

  Institute Of Radiological Sciences National Yang Ming University

• Chang Jui-feng

  Institute Of Radiological Sciences National Yang Ming University

• Chen Jui-lin

  Institute Of Radiological Sciences National Yang Ming University

関連論文

• Differential Gene Expression in a DNA Double-strand-breakRepair Mutant XRS-5 Defective in Ku80: Analysisby cDNA Microarray
• SL-2-2 A study of radiation effects in human p53-mutated and wild-type glioma cells by DNA microarray and qPCR(Radiation Biology Research in Asia, Abstracts of the 46th Annual Meeting of the Japan Radiation Research Society)

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