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PMID:20687897

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Citation

Park, EJ, Hur, SK and Kwon, J (2010) Human INO80 chromatin-remodelling complex contributes to DNA double-strand break repair via the expression of Rad54B and XRCC3 genes. Biochem. J. 431:179-87

Abstract

Recent studies have shown that the SWI/SNF family of ATP-dependent chromatin-remodelling complexes play important roles in DNA repair as well as in transcription. The INO80 complex, the most recently described member of this family, has been shown in yeast to play direct role in DNA DSB (double-strand break) repair without affecting the expression of the genes involved in this process. However, whether this function of the INO80 complex is conserved in higher eukaryotes has not been investigated. In the present study, we found that knockdown of hINO80 (human INO80) confers DNA-damage hypersensitivity and inefficient DSB repair. Microarray analysis and other experiments have identified the Rad54B and XRCC3 (X-ray repair complementing defective repair in Chinese-hamster cells 3) genes, implicated in DSB repair, to be repressed by hINO80 deficiency. Chromatin immunoprecipitation studies have shown that hINO80 binds to the promoters of the Rad54B and XRCC3 genes. Re-expression of the Rad54B and XRCC3 genes rescues the DSB repair defect in hINO80-deficient cells. These results suggest that hINO80 assists DSB repair by positively regulating the expression of the Rad54B and XRCC3 genes. Therefore, unlike yeast INO80, hINO80 can contribute to DSB repair indirectly via gene expression, suggesting that the mechanistic role of this chromatin remodeller in DSB repair is evolutionarily diversified.

Links

PubMed Online version:10.1042/BJ20100988

Keywords

Chromatin Assembly and Disassembly/genetics; DNA Breaks, Double-Stranded; DNA Helicases/deficiency; DNA Helicases/genetics; DNA Helicases/metabolism; DNA Repair/genetics; DNA-Binding Proteins/genetics; Gene Knockdown Techniques; HeLa Cells; Histones/metabolism; Humans; Nuclear Proteins/genetics; Promoter Regions, Genetic/genetics; Protein Binding

Significance

Annotations

Gene product Qualifier GO Term Evidence Code with/from Aspect Extension Notes Status

HUMAN:INO80

GO:0006302: double-strand break repair

ECO:0000316:

UniProtKB:Q9ULG1


P

Figure 1 hINO80 knockdown confers DNA-damage sensitivity and inefficient DSB repair

Figure 4 hINO80 binds to the promoters of the Rad54B and XRCC3 genes

Figure 5 Re-expression of Rad54B and XRCC3 rescues the DSB repair defect in hINO80-deficient cells

complete
CACAO 10387

HUMAN:INO80

involved_in

GO:0006302: double-strand break repair

ECO:0000315: mutant phenotype evidence used in manual assertion

P

Seeded From UniProt

complete

HUMAN:INO80

involved_in

GO:0045944: positive regulation of transcription by RNA polymerase II

ECO:0000315: mutant phenotype evidence used in manual assertion

P

Seeded From UniProt

complete

HUMAN:INO80

involved_in

GO:0071479: cellular response to ionizing radiation

ECO:0000315: mutant phenotype evidence used in manual assertion

P

Seeded From UniProt

complete

Notes

See also

References

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