Chk1 Promotes DNA Damage Response Bypass following Oxidative Stress in a Model of Hydrogen Peroxide-Associated Ulcerative Colitis through JNK Inactivation and Chromatin Binding
Joint Authors
Reissig, Kathrin
Silver, Andrew
Hartig, Roland
Schinlauer, Antje
Walluscheck, Diana
Guenther, Thomas
Siedentopf, Sandra
Ross, Jochen
Vo, Diep-Khanh
Roessner, Albert
Poehlmann-Nitsche, Angela
Source
Oxidative Medicine and Cellular Longevity
Issue
Vol. 2017, Issue 2017 (31 Dec. 2017), pp.1-20, 20 p.
Publisher
Hindawi Publishing Corporation
Publication Date
2017-06-07
Country of Publication
Egypt
No. of Pages
20
Main Subjects
Abstract EN
Dysregulation of c-Jun N-terminal kinase (JNK) activation promoted DNA damage response bypass and tumorigenesis in our model of hydrogen peroxide-associated ulcerative colitis (UC) and in patients with quiescent UC (QUC), UC-related dysplasia, and UC-related carcinoma (UC-CRC), thereby adapting to oxidative stress.
In the UC model, we have observed features of oncogenic transformation: increased proliferation, undetected DNA damage, and apoptosis resistance.
Here, we show that Chk1 was downregulated but activated in the acute and quiescent chronic phases.
In both phases, Chk1 was linked to DNA damage response bypass by suppressing JNK activation following oxidative stress, promoting cell cycle progression despite DNA damage.
Simultaneously, activated Chk1 was bound to chromatin.
This triggered histone acetylation and the binding of histone acetyltransferases and transcription factors to chromatin.
Thus, chromatin-immobilized activated Chk1 executed a dual function by suppressing DNA damage response and simultaneously inducing chromatin modulation.
This caused undetected DNA damage and increased cellular proliferation through failure to transmit the appropriate DNA damage signal.
Findings in vitro were corroborated by chromatin accumulation of activated Chk1, Ac-H3, Ac-H4, and c-Jun in active UC (AUC) in vivo.
Targeting chromatin-bound Chk1, GCN5, PCAF, and p300/CBP could be a novel therapeutic strategy to prevent UC-related tumor progression.
American Psychological Association (APA)
Reissig, Kathrin& Silver, Andrew& Hartig, Roland& Schinlauer, Antje& Walluscheck, Diana& Guenther, Thomas…[et al.]. 2017. Chk1 Promotes DNA Damage Response Bypass following Oxidative Stress in a Model of Hydrogen Peroxide-Associated Ulcerative Colitis through JNK Inactivation and Chromatin Binding. Oxidative Medicine and Cellular Longevity،Vol. 2017, no. 2017, pp.1-20.
https://search.emarefa.net/detail/BIM-1196481
Modern Language Association (MLA)
Reissig, Kathrin…[et al.]. Chk1 Promotes DNA Damage Response Bypass following Oxidative Stress in a Model of Hydrogen Peroxide-Associated Ulcerative Colitis through JNK Inactivation and Chromatin Binding. Oxidative Medicine and Cellular Longevity No. 2017 (2017), pp.1-20.
https://search.emarefa.net/detail/BIM-1196481
American Medical Association (AMA)
Reissig, Kathrin& Silver, Andrew& Hartig, Roland& Schinlauer, Antje& Walluscheck, Diana& Guenther, Thomas…[et al.]. Chk1 Promotes DNA Damage Response Bypass following Oxidative Stress in a Model of Hydrogen Peroxide-Associated Ulcerative Colitis through JNK Inactivation and Chromatin Binding. Oxidative Medicine and Cellular Longevity. 2017. Vol. 2017, no. 2017, pp.1-20.
https://search.emarefa.net/detail/BIM-1196481
Data Type
Journal Articles
Language
English
Notes
Includes bibliographical references
Record ID
BIM-1196481