A method for systematic mapping of protein lysine methylation identifies functions for HP1β in DNA damage response

Huadong Liu, Marek Galka, Eiichiro Mori, Xuguang Liu, Yu fen Lin, Ran Wei, Paula Pittock, Courtney Voss, Gurpreet Dhami, Xing Li, Masaaki Miyaji, Gilles Lajoie, Benjamin Chen, ShawnShun Cheng Li

Research output: Contribution to journalArticle

66 Scopus citations

Abstract

Lysine methylation occurs on both histone and nonhistone proteins. However, our knowledge on the prevalence and function of nonhistone protein methylation is poor. We describe an approach that combines peptide array, bioinformatics, and mass spectrometry to systematically identify lysine methylation sites and map methyllysine-driven protein-protein interactions. Using this approach, we identified a high-confidence and high-resolution interactome of the heterochromatin protein 1β (HP1β) and uncovered, simultaneously, numerous methyllysine sites on nonhistone proteins. We found that HP1β binds to DNA-dependent protein kinase catalytic subunit (DNA-PKcs) and regulates its localization to double-strand breaks (DSBs) during DNA damage response (DDR). Mutation of the methylation sites in DNA-PKcs or depletion of HP1β in cells caused defects in DDR. Furthermore, we showed that the methylation of DNA-PKcs and many other proteins in the HP1β interactome undergoes large changes in response to DNA damage, indicating that Lys methylation is a highly dynamic posttranslational modification.

Original languageEnglish (US)
Pages (from-to)723-735
Number of pages13
JournalMolecular cell
Volume50
Issue number5
DOIs
StatePublished - Jun 6 2013

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ASJC Scopus subject areas

  • Molecular Biology
  • Cell Biology

Cite this

Liu, H., Galka, M., Mori, E., Liu, X., Lin, Y. F., Wei, R., Pittock, P., Voss, C., Dhami, G., Li, X., Miyaji, M., Lajoie, G., Chen, B., & Li, S. C. (2013). A method for systematic mapping of protein lysine methylation identifies functions for HP1β in DNA damage response. Molecular cell, 50(5), 723-735. https://doi.org/10.1016/j.molcel.2013.04.025