Methylation of histone H3 lysine 36 enhances DNA repair by nonhomologous end-joining.

Sheema Fnu, Elizabeth A. Williamson, Leyma P. De Haro, Mark Brenneman, Justin Wray, Montaser Shaheen, Krishnan Radhakrishnan, Suk-Hee Lee, Jac A. Nickoloff, Robert Hromas

Research output: Contribution to journalArticle

119 Citations (Scopus)

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.

Original languageEnglish (US)
Pages (from-to)540-545
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Volume108
Issue number2
DOIs
StatePublished - Jan 11 2011
Externally publishedYes

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DNA End-Joining Repair
Histones
Methylation
Lysine
DNA Repair
Double-Stranded DNA Breaks
Recombinational DNA Repair
Genomic Instability
Ionizing Radiation
Maintenance

ASJC Scopus subject areas

  • General

Cite this

Methylation of histone H3 lysine 36 enhances DNA repair by nonhomologous end-joining. / Fnu, Sheema; Williamson, Elizabeth A.; De Haro, Leyma P.; Brenneman, Mark; Wray, Justin; Shaheen, Montaser; Radhakrishnan, Krishnan; Lee, Suk-Hee; Nickoloff, Jac A.; Hromas, Robert.

In: Proceedings of the National Academy of Sciences of the United States of America, Vol. 108, No. 2, 11.01.2011, p. 540-545.

Research output: Contribution to journalArticle

Fnu, S, Williamson, EA, De Haro, LP, Brenneman, M, Wray, J, Shaheen, M, Radhakrishnan, K, Lee, S-H, Nickoloff, JA & Hromas, R 2011, 'Methylation of histone H3 lysine 36 enhances DNA repair by nonhomologous end-joining.', Proceedings of the National Academy of Sciences of the United States of America, vol. 108, no. 2, pp. 540-545. https://doi.org/10.1073/pnas.1013571108
Fnu, Sheema ; Williamson, Elizabeth A. ; De Haro, Leyma P. ; Brenneman, Mark ; Wray, Justin ; Shaheen, Montaser ; Radhakrishnan, Krishnan ; Lee, Suk-Hee ; Nickoloff, Jac A. ; Hromas, Robert. / Methylation of histone H3 lysine 36 enhances DNA repair by nonhomologous end-joining. In: Proceedings of the National Academy of Sciences of the United States of America. 2011 ; Vol. 108, No. 2. pp. 540-545.
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