Recruitment of lysine demethylase 2A to DNA double strand breaks and its interaction with 53BP1 ensures genome stability.

ABSTRACT: Lysine demethylase 2A (KDM2A) functions in transcription as a demethylase of lysine 36 on histone H3. Herein, we characterise a role for KDM2A in the DNA damage response in which KDM2A stimulates conjugation of ubiquitin to 53BP1. Impaired KDM2A-mediated ubiquitination negatively affects the recruitment of 53BP1 to DSBs. Notably, we show that KDM2A itself is recruited to DSBs in a process that depends on its demethylase activity and zinc finger domain. Moreover, we show that KDM2A plays an important role in ensuring genomic stability upon DNA damage. Depletion of KDM2A or disruption of its zinc finger domain results in the accumulation of micronuclei following ionizing radiation (IR) treatment. In addition, IR-treated cells depleted of KDM2A display premature exit from the G2/M checkpoint.

SUBMITTER: Bueno MTD 

PROVIDER: S-EPMC5882307 | biostudies-literature | 2018 Mar

REPOSITORIES: biostudies-literature