DNA damage response and cancer therapeutics through the lens of the Fanconi Anemia DNA repair pathway

Bhattacharjee, S., Nandi, S. (October 2017) DNA damage response and cancer therapeutics through the lens of the Fanconi Anemia DNA repair pathway. Cell Commun Signal, 15 (1). p. 41. ISSN 1478-811x

URL: https://www.ncbi.nlm.nih.gov/pubmed/29017571
DOI: 10.1186/s12964-017-0195-9

Abstract

Fanconi Anemia (FA) is a rare, inherited genomic instability disorder, caused by mutations in genes involved in the repair of interstrand DNA crosslinks (ICLs). The FA signaling network contains a unique nuclear protein complex that mediates the monoubiquitylation of the FANCD2 and FANCI heterodimer, and coordinates activities of the downstream DNA repair pathway including nucleotide excision repair, translesion synthesis, and homologous recombination. FA proteins act at different steps of ICL repair in sensing, recognition and processing of DNA lesions. The multi-protein network is tightly regulated by complex mechanisms, such as ubiquitination, phosphorylation, and degradation signals that are critical for the maintenance of genome integrity and suppressing tumorigenesis. Here, we discuss recent advances in our understanding of how the FA proteins participate in ICL repair and regulation of the FA signaling network that assures the safeguard of the genome. We further discuss the potential application of designing small molecule inhibitors that inhibit the FA pathway and are synthetic lethal with DNA repair enzymes that can be used for cancer therapeutics.

Item Type: Paper
Uncontrolled Keywords: Cancer therapeutics Combination Therapy Genomic instability DNA damage response DNA repair Fanconi Anemia (FA) signaling network Homologous recombination Interstrand crosslink (ICL) Synthetic lethality Translesion synthesis
Subjects: diseases & disorders > cancer
bioinformatics > genomics and proteomics > genetics & nucleic acid processing > DNA, RNA structure, function, modification > DNA repair
diseases & disorders > cancer > drugs and therapies
CSHL Authors:
Communities: CSHL labs > Martienssen lab
CSHL labs > Stillman lab
Depositing User: Matt Covey
Date: 10 October 2017
Date Deposited: 12 Oct 2017 19:36
Last Modified: 12 Oct 2017 19:36
Related URLs:
URI: http://repository.cshl.edu/id/eprint/35570

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