TY - JOUR
T1 - A method for systematic mapping of protein lysine methylation identifies functions for HP1β in DNA damage response
AU - Liu, Huadong
AU - Galka, Marek
AU - Mori, Eiichiro
AU - Liu, Xuguang
AU - Lin, Yu fen
AU - Wei, Ran
AU - Pittock, Paula
AU - Voss, Courtney
AU - Dhami, Gurpreet
AU - Li, Xing
AU - Miyaji, Masaaki
AU - Lajoie, Gilles
AU - Chen, Benjamin
AU - Li, Shawn Shun Cheng
PY - 2013/6/6
Y1 - 2013/6/6
N2 - 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.
AB - 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.
UR - https://www.scopus.com/pages/publications/84878825857
U2 - 10.1016/j.molcel.2013.04.025
DO - 10.1016/j.molcel.2013.04.025
M3 - 文章
C2 - 23707759
AN - SCOPUS:84878825857
SN - 1097-2765
VL - 50
SP - 723
EP - 735
JO - Molecular Cell
JF - Molecular Cell
IS - 5
ER -