GONUTS has been updated to MW1.31 Most things seem to be working but be sure to report problems.

Have any questions? Please email us at ecoliwiki@gmail.com

PMID:21187428

From GONUTS
Jump to: navigation, search
Citation

Fnu, S, Williamson, EA, De Haro, LP, Brenneman, M, Wray, J, Shaheen, M, Radhakrishnan, K, Lee, SH, Nickoloff, JA and Hromas, R (2011) Methylation of histone H3 lysine 36 enhances DNA repair by nonhomologous end-joining. Proc. Natl. Acad. Sci. U.S.A. 108:540-5

Abstract

Given its significant role in the maintenance of genomic stability, histone methylation has been postulated to regulate DNA repair. Histone methylation mediates localization of 53BP1 to a DNA double-strand break (DSB) during homologous recombination repair, but a role in DSB repair by nonhomologous end-joining (NHEJ) has not been defined. By screening for histone methylation after DSB induction by ionizing radiation we found that generation of dimethyl histone H3 lysine 36 (H3K36me2) was the major event. Using a novel human cell system that rapidly generates a single defined DSB in the vast majority of cells, we found that the DNA repair protein Metnase (also SETMAR), which has a SET histone methylase domain, localized to an induced DSB and directly mediated the formation of H3K36me2 near the induced DSB. This dimethylation of H3K36 improved the association of early DNA repair components, including NBS1 and Ku70, with the induced DSB, and enhanced DSB repair. In addition, expression of JHDM1a (an H3K36me2 demethylase) or histone H3 in which K36 was mutated to A36 or R36 to prevent H3K36me2 formation decreased the association of early NHEJ repair components with an induced DSB and decreased DSB repair. Thus, these experiments define a histone methylation event that enhances DNA DSB repair by NHEJ.

Links

PubMed PMC3021059 Online version:10.1073/pnas.1013571108

Keywords

Antigens, Nuclear/chemistry; Cell Line, Tumor; DNA Breaks, Double-Stranded; DNA Methylation; DNA Repair; DNA Restriction Enzymes/pharmacology; DNA-Binding Proteins/chemistry; Deoxyribonucleases, Type II Site-Specific/pharmacology; Dimerization; Gene Expression Regulation, Neoplastic; Histone-Lysine N-Methyltransferase/chemistry; Histone-Lysine N-Methyltransferase/metabolism; Histones/chemistry; Humans; Lysine/chemistry; Models, Theoretical; Reverse Transcriptase Polymerase Chain Reaction; Saccharomyces cerevisiae Proteins/pharmacology; Time Factors

Significance

Annotations

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

HUMAN:SETMR

located_in

GO:0035861: site of double-strand break

ECO:0000314: direct assay evidence used in manual assertion

C

Seeded From UniProt

complete

HUMAN:KDM2A

involved_in

GO:0006303: double-strand break repair via nonhomologous end joining

ECO:0000315: mutant phenotype evidence used in manual assertion

P

Seeded From UniProt

complete

HUMAN:KDM2A

involved_in

GO:0070544: histone H3-K36 demethylation

ECO:0000315: mutant phenotype evidence used in manual assertion

P

Seeded From UniProt

complete

HUMAN:SETMR

part_of

GO:0035861: site of double-strand break

ECO:0000314: direct assay evidence used in manual assertion

C

Seeded From UniProt

complete

HUMAN:SETMR

involved_in

GO:0097676: histone H3-K36 dimethylation

ECO:0000315: mutant phenotype evidence used in manual assertion

P

Seeded From UniProt

complete

HUMAN:SETMR

involved_in

GO:0006303: double-strand break repair via nonhomologous end joining

ECO:0000315: mutant phenotype evidence used in manual assertion

P

Seeded From UniProt

complete

Notes

See also

References

See Help:References for how to manage references in GONUTS.