Human CtIP: A 'double agent' in DNA repair and tumorigenesis.

Abstract Human CtIP was originally identified as an interactor of the retinoblastoma protein and BRCA1, two bona fide tumour suppressors frequently mutated in cancer. CtIP is renowned for its role in the resection of DNA double-strand breaks (DSBs) during homologous recombination, a largely error-free DNA repair pathway crucial in maintaining genome integrity. However, CtIP-dependent DNA end resection is equally accountable for alternative end-joining, a mutagenic DSB repair mechanism implicated in oncogenic chromosomal translocations. In addition, CtIP contributes to transcriptional regulation of G1/S transition, DNA damage checkpoint signalling, and replication fork protection pathways. In this review, we present a perspective on the current state of knowledge regarding the tumour-suppressive and oncogenic properties of CtIP and provide an overview of their relevance for cancer development, progression, and therapy.