PARP1-dependent recruitment of KDM4D histone demethylase to DNA damage sites promotes double-strand break repair
Abstract
Sophisticated DNA damage repair mechanisms are required to fix DNA lesions and preserve the integrity of the genome. This manuscript provides characterization of KDM4D role in promoting the repair of double-strand breaks (DSBs). Our findings show that KDM4D lysine demethylase is swiftly recruited to DNA breakage sites via its C-terminal region in a PARP1-dependent manner. Further, we have uncovered an exciting function of KDM4D in regulating the association of the DNA damage response master kinase, ATM, with chromatin, thus explaining the defective phosphorylation of ATM substrates found in KDM4D-depleted cells. Altogether, this study advances our understanding of the molecular mechanisms that regulate the repair of DSBs, a critical pathway that is essential for maintaining genome integrity.
- Publication:
-
Proceedings of the National Academy of Science
- Pub Date:
- February 2014
- DOI:
- 10.1073/pnas.1317585111
- Bibcode:
- 2014PNAS..111E.728K