FANCI functions as a repair/apoptosis switch in response to DNA crosslinks

Author(s):  
Richa B. Shah ◽  
Jennifer L. Kernan ◽  
Anya van Hoogstraten ◽  
Kiyohiro Ando ◽  
Yuanyuan Li ◽  
...  
Keyword(s):  

2020 ◽  
Vol 22 (Supplement_3) ◽  
pp. iii414-iii414
Author(s):  
Shigeo Ohba ◽  
Yuichi Hirose

Abstract Diffuse midline glioma, H3 K27M-mutant (DMG) is a newly defined entity. The prognosis of DMG is poor. Because surgical resection is often incomplete for DMG, radiotherapy and chemotherapy are important. Temozolomide (TMZ) is an alkylating agent that adds a methyl group to DNA (O6-guanine, N7-guanine, and N3-adenine). TMZ-induced cytotoxicity is mainly derived from O6-methylguanine, which is repaired by O6-methylguanine DNA methyltransferase (MGMT). It has been reported that most of DMG lacked MGMT promoter hypermethylation, which is thought to contribute to less effectiveness of TMZ to DMG. The purpose of the study is to explore the way to inhibit the proliferation of DMG. A DMG cell line, SF8628, was used for the experiments. SF8628 had the expression of MGMT and was revealed to be resistant to TMZ. Because N7-methylguanine and N3-methyladenine are repaired via base excision repair, poly (adenosine diphosphate-ribose) polymerase (PARP) inhibitor combined with TMZ was considered to be effective to suppress the proliferation of SF8628. As expected, PARP inhibitor enhanced TMZ-induced cytotoxicity in SF8628. Dianhydrogalactiol (DAG) is a bifunctional DNA-targeting agent forming N7-alkylguanine and inter-strand DNA crosslinks. DAG reduced the clonogenicity of SF8628. Moreover, inhibition of homologous recombination enhanced the DAG-induced cytotoxicity in SF8629. The combination treatment of PARP inhibitor and TMZ, or DAG were revealed to be promising treatments in SF8628.



2006 ◽  
Vol 72 (1) ◽  
pp. 11-18 ◽  
Author(s):  
M. Emmons ◽  
D. Boulware ◽  
D.M. Sullivan ◽  
L.A. Hazlehurst


1993 ◽  
Vol 212 (2) ◽  
pp. 402-406 ◽  
Author(s):  
R. Batel ◽  
M. Vukmirovic ◽  
N. Bihari ◽  
R.K. Zahn ◽  
W.E.G. Muller




Author(s):  
Stefan Pfuhler ◽  
Sieglinde Deutschenbaur ◽  
Hans-Uwe Wolf


2006 ◽  
Vol 25 (20) ◽  
pp. 4921-4932 ◽  
Author(s):  
Katsuhiro Hanada ◽  
Magda Budzowska ◽  
Mauro Modesti ◽  
Alex Maas ◽  
Claire Wyman ◽  
...  
Keyword(s):  


2019 ◽  
Vol 61 (4) ◽  
Author(s):  
U. Aliyaskarova ◽  
M. Saparbaev ◽  
Bissenbaev A


2004 ◽  
Vol 126 (1) ◽  
pp. 104-110 ◽  
Author(s):  
David C. Lin ◽  
Bernard Yurke ◽  
Noshir A. Langrana

Mechanical properties of a polyacrylamide gel with reversible DNA crosslinks are presented. In this system, three DNA strands replace traditional chemical crosslinkers. In contrast to thermoset chemically crosslinked polyacrylamide, the new hydrogel is thermoreversible; crosslink dissociation without the addition of heat is also feasible by introducing a specific removal DNA strand. This hydrogel is characterized by a critical crosslink concentration at which gelation occurs. Below the critical point, a characteristic temperature exists at which a transition in viscosity is observed. Both temperature-dependent viscosity and elastic modulus of the material are functions of crosslink density.



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