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PMID:20855601

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Citation

Jiang, Y, Wang, X, Bao, S, Guo, R, Johnson, DG, Shen, X and Li, L (2010) INO80 chromatin remodeling complex promotes the removal of UV lesions by the nucleotide excision repair pathway. Proc. Natl. Acad. Sci. U.S.A. 107:17274-9

Abstract

The creation of accessible DNA in the context of chromatin is a key step in many DNA functions. To reveal how ATP-dependent chromatin remodeling activities impact DNA repair, we constructed mammalian genetic models for the INO80 chromatin remodeling complex and investigated the impact of loss of INO80 function on the repair of UV-induced photo lesions. We showed that deletion of two core components of the INO80 complex, INO80 and ARP5, significantly hampered cellular removal of UV-induced photo lesions but had no significant impact on the transcription of nucleotide excision repair (NER) factors. Loss of INO80 abolished the assembly of NER factors, suggesting that prior chromatin relaxation is important for the NER incision process. Ino80 and Arp5 are enriched to UV-damaged DNA in an NER-incision-independent fashion, suggesting that recruitment of the remodeling activity likely takes place during the initial stage of damage recognition. These results demonstrate a critical role of INO80 in creating DNA accessibility for the NER pathway and provide direct evidence that repair of UV lesions and perhaps most bulky adduct lesions requires chromatin reconfiguration.

Links

PubMed PMC2951448 Online version:10.1073/pnas.1008388107

Keywords

Chromatin Assembly and Disassembly; DNA/genetics; DNA/metabolism; DNA/radiation effects; DNA Damage; DNA Repair; Gene Knockdown Techniques; Protein Subunits/genetics; Protein Subunits/metabolism; Saccharomyces cerevisiae/drug effects; Saccharomyces cerevisiae/genetics; Saccharomyces cerevisiae/metabolism; Saccharomyces cerevisiae Proteins/genetics; Saccharomyces cerevisiae Proteins/metabolism; Ultraviolet Rays

Significance

Annotations

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

HUMAN:DDB1

enables

GO:0005515: protein binding

ECO:0000353: physical interaction evidence used in manual assertion

UniProtKB:Q9H9F9

F

Seeded From UniProt

complete

HUMAN:DDB1

enables

GO:0005515: protein binding

ECO:0000353: physical interaction evidence used in manual assertion

UniProtKB:Q9ULG1

F

Seeded From UniProt

complete

HUMAN:ARP5

involved_in

GO:0070914: UV-damage excision repair

ECO:0000315: mutant phenotype evidence used in manual assertion

P

Seeded From UniProt

complete

HUMAN:ARP5

enables

GO:0005515: protein binding

ECO:0000353: physical interaction evidence used in manual assertion

UniProtKB:Q16531

F

Seeded From UniProt

complete

HUMAN:ARP5

enables

GO:0005515: protein binding

ECO:0000353: physical interaction evidence used in manual assertion

UniProtKB:Q9ULG1

F

Seeded From UniProt

complete

HUMAN:INO80

enables

GO:0005515: protein binding

ECO:0000353: physical interaction evidence used in manual assertion

UniProtKB:Q16531

F

Seeded From UniProt

complete

HUMAN:INO80

enables

GO:0005515: protein binding

ECO:0000353: physical interaction evidence used in manual assertion

UniProtKB:Q9H9F9

F

Seeded From UniProt

complete

HUMAN:INO80

involved_in

GO:0070914: UV-damage excision repair

ECO:0000315: mutant phenotype evidence used in manual assertion

P

Seeded From UniProt

complete

Notes

See also

References

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