Ku70 Corrupts DNA Repair in the Absence of the Fanconi Anemia Pathway

Science ◽  
2010 ◽  
Vol 329 (5988) ◽  
pp. 219-223 ◽  
Author(s):  
P. Pace ◽  
G. Mosedale ◽  
M. R. Hodskinson ◽  
I. V. Rosado ◽  
M. Sivasubramaniam ◽  
...  
Keyword(s):  
Dna Repair ◽  
Fanconi Anemia ◽  
Fanconi Anemia Pathway

scholarly journals Inhibition of USP28 overcomes Cisplatin-Resistance of Squamous Tumors by Suppression of the Fanconi Anemia Pathway

2020 ◽  
Author(s):  
Cristian Prieto-Garcia ◽  
Oliver Hartmann ◽  
Michaela Reissland ◽  
Thomas Fischer ◽  
Carina R. Maier ◽  
...  
Keyword(s):  
Dna Damage ◽  
Dna Repair ◽  
Tumor Cells ◽  
Dna Damage Response ◽  
Fanconi Anemia ◽  
Cisplatin Resistance ◽  
Chemotherapy Resistance ◽  
Fanconi Anemia Pathway ◽  
Platinum Based Chemotherapy ◽  
Damage Response

AbstractSquamous cell carcinomas (SCC) frequently have a limited response to or develop resistance to platinum-based chemotherapy, and have an exceptionally high tumor mutational burden. As a consequence, overall survival is limited and novel therapeutic strategies are urgently required, especially in light of a rising incidences. SCC tumors express ΔNp63, a potent regulator of the Fanconi Anemia (FA) DNA-damage response pathway during chemotherapy, thereby directly contributing to chemotherapy-resistance. Here we report that the deubiquitylase USP28 affects the FA DNA repair pathway during cisplatin treatment in SCC, thereby influencing therapy outcome. In an ATR-dependent fashion, USP28 is phosphorylated and activated to positively regulate the DNA damage response. Inhibition of USP28 reduces recombinational repair via an ΔNp63-Fanconi Anemia pathway axis, and weakens the ability of tumor cells to accurately repair DNA. Our study presents a novel mechanism by which tumor cells, and in particular ΔNp63 expressing SCC, can be targeted to overcome chemotherapy resistance.SignificanceLimited treatment options and low response rates to chemotherapy are particularly common in patients with squamous cancer. The SCC specific transcription factor ΔNp63 enhances the expression of Fanconi Anemia genes, thereby contributing to recombinational DNA repair and Cisplatin resistance. Targeting the USP28-ΔNp63 axis in SCC tones down this DNA damage response pathways, thereby sensitizing SCC cells to cisplatin treatment.

scholarly journals The Fanconi Anemia Pathway of DNA Repair and Human Cancer

10.5772/59995 ◽  
2015 ◽  
Author(s):  
Vaidehi Krishnan ◽  
Lavina Sierra Tay ◽  
Yoshiaki Ito
Keyword(s):  
Dna Repair ◽  
Fanconi Anemia ◽  
Human Cancer ◽  
Fanconi Anemia Pathway

scholarly journals RUNX Poly(ADP-Ribosyl)ation and BLM Interaction Facilitate the Fanconi Anemia Pathway of DNA Repair

Cell Reports ◽  
2018 ◽  
Vol 24 (7) ◽  
pp. 1747-1755 ◽  
Author(s):  
Lavina Sierra Tay ◽  
Vaidehi Krishnan ◽  
Haresh Sankar ◽  
Yu Lin Chong ◽  
Linda Shyue Huey Chuang ◽  
...  
Keyword(s):  
Dna Repair ◽  
Fanconi Anemia ◽  
Fanconi Anemia Pathway

scholarly journals The role of the Fanconi anemia pathway in DNA repair and maintenance of genome stability

2014 ◽  
Vol 68 ◽  
pp. 459-472 ◽  
Author(s):  
Aleksandra M. Koczorowska ◽  
Aneta Białkowska ◽  
Katarzyna Kluzek ◽  
Małgorzata Z. Zdzienicka
Keyword(s):  
Dna Repair ◽  
Fanconi Anemia ◽  
Genome Stability ◽  
Fanconi Anemia Pathway
Sign in / Sign up

Export Citation Format

Share Document