title: The emerging role of lysine demethylases in DNA damage response: dissecting the recruitment mode of KDM4D/JMJD2D to DNA damage sites.
abstract: KDM4D is a lysine demethylase that removes tri- and di- methylated residues from H3K9 and is involved in transcriptional regulation and carcinogenesis. We recently showed that KDM4D is recruited to DNA damage sites in a PARP1-dependent manner and facilitates double-strand break repair in human cells. Moreover, we demonstrated that KDM4D is an RNA binding protein and mapped its RNA-binding motifs. Interestingly, KDM4D-RNA interaction is essential for its localization on chromatin and subsequently for efficient demethylation of its histone substrate H3K9me3. Here, we provide new data that shed mechanistic insights into KDM4D accumulation at DNA damage sites. We show for the first time that KDM4D binds poly(ADP-ribose) (PAR) in vitro via its C-terminal region. In addition, we demonstrate that KDM4D-RNA interaction is required for KDM4D accumulation at DNA breakage sites. Finally, we discuss the recruitment mode and the biological functions of additional lysine demethylases including KDM4B, KDM5B, JMJD1C, and LSD1 in DNA damage response.
authors.affiliation: a Department of Biology ; Israel Institute of Technology ; Haifa , Israel.
authors.forename: Hanan
authors.initials: H
authors.lastname: Khoury-Haddad
authors.forename: Prathamesh T
authors.initials: PT
authors.lastname: Nadar-Ponniah
authors.forename: Samah
authors.initials: S
authors.lastname: Awwad
authors.forename: Nabieh
authors.initials: N
authors.lastname: Ayoub
mesh_terms: D001665:Binding Sites; D045744:Cell Line, Tumor; D004249:DNA Damage; D004260:DNA Repair; D042822:Genomic Instability; D006801:Humans; D056484:Jumonji Domain-Containing Histone Demethylases / Q000378:metabolism*; D011485:Protein Binding; D021381:Protein Transport; D022661:RNA, Untranslated / Q000378:metabolism
chemical_list: D022661:RNA, Untranslated; D056484:Jumonji Domain-Containing Histone Demethylases; C521694:KDM4D protein, human
keywords: DNA damage response (DDR); KDM4D; PARP1; and cancer; chromosomal instability; double strand break (DSB); lysine demethylases (KDM); poly(ADP-ribose)ylation (PARylation)