The histone demethylase LSD1/KDM1A promotes the DNA damage response

• DOI: 10.1083/jcb.201302092
• Publication Date: 2013-11-11T21:59:25Z
• Authors: Nima Mosammaparast; Haeyoung Kim; Benoit Laurent; Yu Zhao; Hui Jun Lim; Mona C. Majid; Sebastian Dango; Yuying Luo; Kristina Hempel; Mathew E. Sowa; Steven P. Gygi; Hanno Steen; J. Wade Harper; Bruce Yankner; Yang Shi
• Keywords: Demethylase

Histone demethylation is known to regulate transcription, but its role in other processes largely unknown. We report a for the histone demethylase LSD1/KDM1A DNA damage response (DDR). show that LSD1 recruited directly sites of damage. H3K4 dimethylation, major substrate LSD1, reduced at an LSD1-dependent manner. The E3 ubiquitin ligase RNF168 physically interacts with and we find this interaction be important recruitment sites. Although loss did not affect initial formation pH2A.X foci, 53BP1 BRCA1 complex were upon knockdown. Mechanistically, was likely result compromised ubiquitylation preferentially late S/G2. Consistent DDR, knockdown resulted moderate hypersensitivity γ-irradiation increased homologous recombination. Our findings uncover direct DDR place downstream pathway.