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

Nour L Mozaffari; Fabio Pagliarulo; Alessandro A Sartori

doi:10.1016/j.semcdb.2020.09.001

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

Semin Cell Dev Biol. 2021 May:113:47-56. doi: 10.1016/j.semcdb.2020.09.001. Epub 2020 Sep 17.

Authors

Nour L Mozaffari¹, Fabio Pagliarulo¹, Alessandro A Sartori²

Affiliations

¹ Institute of Molecular Cancer Research, University of Zurich, Zurich, Switzerland.
² Institute of Molecular Cancer Research, University of Zurich, Zurich, Switzerland. Electronic address: sartori@imcr.uzh.ch.

PMID: 32950401
DOI: 10.1016/j.semcdb.2020.09.001

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.

Keywords: BRCA1; CtIP/RBBP8; DNA end resection; double-strand break repair; genome instability; pancreatic cancer; replication stress; synthetic lethality; transcriptional regulation; tumour suppressor.

Publication types

Research Support, Non-U.S. Gov't
Research Support, U.S. Gov't, Non-P.H.S.
Review

MeSH terms

Carcinogenesis / genetics*
DNA Repair / genetics*
Humans