Implication of HIC1 (Hypermethylated In Cancer 1) in the DNA damage response

HIC1 (Hypermethylated In Cancer 1) is a tumor suppressor gene which is epigenetically inactivated in many human cancers. HIC1 encodes a transcriptional repressor comprising an N-terminal BTB/POZ domain and a C-terminal DNA binding domain containing five Kruppel-like C2H2 zinc fingers. To date, few HIC1 target genes are known and the regulation of HIC1 activity is not fully deciphered. However, a growing list of studies, summarized in this review, strongly suggest that HIC1 plays a central role in the DNA damage response through the establishment of several complex regulatory loops involving HIC1, p53, SIRT1 and E2F1. triangle