| Title | Histone demethylase KDM5B is a key regulator of genome stability |
| Authors | Li, Xin Liu, Ling Yang, Shangda Song, Nan Zhou, Xing Gao, Jie Yu, Na Shan, Lin Wang, Qian Liang, Jing Xuan, Chenghao Wang, Yan Shang, Yongfeng Shi, Lei |
| Affiliation | Tianjin Med Univ, Dept Biochem & Mol Biol, Collaborat Innovat Ctr Tianjin Med Epigenet 2011, Tianjin Key Lab Med Epigenet, Tianjin 300070, Peoples R China. Peking Univ Hlth Sci Ctr, Dept Biochem & Mol Biol, Key Lab Carcinogenesis & Translat Res, Minist Educ, Beijing 100191, Peoples R China. |
| Keywords | chromatin modification histone methylation genome maintenance DOUBLE-STRAND BREAKS DNA-DAMAGE RESPONSE REPAIR PROTEINS NUCLEAR ARCHITECTURE CHROMATIN METHYLATION CANCER CELLS ACCUMULATION GAMMA-H2AX |
| Issue Date | 2014 |
| Publisher | proceedings of the national academy of sciences of the united states of america |
| Citation | PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA.2014,111,(19),7096-7101. |
| Abstract | Maintenance of genomic stability is essential for normal organismal development and is vital to prevent diseases such as cancer. As genetic information is packaged into chromatin, it has become increasingly clear that the chromatin environment plays an important role in DNA damage response. However, how DNA repair is controlled by epigenetic mechanisms is not fully understood. Here we report the identification and characterization of lysine-specific histone demethylase 5B (KDM5B), a member of the JmjC domain-containing histone demethylases, as an important player in multiple aspects of DNA double-strand break (DSB) response in human cells. We found that KDM5B becomes enriched in DNA-damage sites after ironizing radiation and endonuclease treatment in a poly(ADP ribose) polymerase 1- and histone variant macroH2A1.1-dependent manner. We showed that KDM5B is required for efficient DSB repair and for the recruitment of Ku70 and BRCA1, the essential component of nonhomologous end-joining and homologous recombination, respectively. Significantly, KDM5B deficiency disengages the DNA repair process, promotes spontaneous DNA damage, activates p53 signaling, and sensitizes cells to genotoxic insults. Our results suggest that KDM5B is a bona fide DNA damage response protein and indicate that KDM5B is an important genome caretaker and a critical regulator of genome stability, adding to the understanding of the roles of epigenetics in the maintenance of genetic fidelity. |
| URI | http://hdl.handle.net/20.500.11897/189266 |
| ISSN | 0027-8424 |
| DOI | 10.1073/pnas.1324036111 |
| Indexed | SCI(E) PubMed |
| Appears in Collections: | 医学部待认领 |
