In response to DNA damages, the ATM-Chk2 pathway is rapidly activated following by phosphorylating a number of proteins such γH2AX, Mre11-Rad50-Nbs1 (MRN) complex , p53 and BRCA1, which are involved in cell cycle arrest, apoptosis and DNA repair to maintain genomic integrity.
CTCF has been demonstrated to participate in DNA damage repair in addition to various cellular progresses including transcription, insulation, and chromatin architecture but how CTCF is recruited into damaged DNA is still vague. In this study, I showed that recruitment and stable retention of CTCF into DNA lesions are dependent on Chk2 kinase activity but neither ATM kinase nor PARP activity. I also mutated five putative CHK2 phosphorylation serine/threonine to alanine residues in CTCF and evaluated recruitments of these CTCF mutants into damaged DNA sites using micro-irradiation. These putative un-phosphorylatable CTCF mutants are less recruited into the sites of damaged DNA, compared with its wild type In particular, ATM is required for CTCF accumulation at damaged DNA sites, although ATM kinase activity is not necessary. HP1γ and KAP-1 attendance into DNA double-strand break are dependent on CTCF. Finally, both N terminal and zinc finger domains are sufficient to CTCF accumulation on a damaged DNA line of the laser.
