Cell Communication and Signaling | |
DNA damage response and cancer therapeutics through the lens of the Fanconi Anemia DNA repair pathway | |
Review | |
Saikat Nandi1  Sonali Bhattacharjee1  | |
[1] Cold Spring Harbor Laboratory, New York, USA; | |
关键词: DNA repair; Fanconi Anemia (FA) signaling network; DNA damage response; Cancer therapeutics; Synthetic lethality; Combination Therapy Genomic instability; Interstrand crosslink (ICL); Homologous recombination; Translesion synthesis; | |
DOI : 10.1186/s12964-017-0195-9 | |
received in 2017-08-01, accepted in 2017-10-03, 发布年份 2017 | |
来源: Springer | |
【 摘 要 】
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.
【 授权许可】
CC BY
© The Author(s). 2017
【 预 览 】
Files | Size | Format | View |
---|---|---|---|
RO202311106906539ZK.pdf | 1205KB | download |
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