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Interference with DNA repair after ionizing radiation by a pyrrole-imidazole polyamide.

التفاصيل البيبلوغرافية
العنوان: Interference with DNA repair after ionizing radiation by a pyrrole-imidazole polyamide.
المؤلفون: Silvia Diaz-Perez, Nathanael Kane, Alexis A Kurmis, Fei Yang, Nicolas T Kummer, Peter B Dervan, Nicholas G Nickols
المصدر: PLoS ONE, Vol 13, Iss 5, p e0196803 (2018)
بيانات النشر: Public Library of Science (PLoS), 2018.
سنة النشر: 2018
المجموعة: LCC:Medicine
LCC:Science
مصطلحات موضوعية: Medicine, Science
الوصف: Pyrrole-imidazole (Py-Im) polyamides are synthetic non-genotoxic minor groove-binding small molecules. We hypothesized that Py-Im polyamides can modulate the cellular response to ionizing radiation. Pre-treatment of cells with a Py-Im polyamide prior to exposure to ionizing radiation resulted in a delay in resolution of phosphorylated γ-H2AX foci, increase in XRCC1 foci, and reduced cellular replication potential. RNA-sequencing of cell lines exposed to the polyamide showed induction of genes related to the ultraviolet radiation response. We observed that the polyamide is almost 10-fold more toxic to a cell line deficient in DNA ligase 3 as compared to the parental cell line. Alkaline single cell gel electrophoresis reveals that the polyamide induces genomic fragmentation in the ligase 3 deficient cell line but not the corresponding parental line. The polyamide interferes directly with DNA ligation in vitro. We conclude that Py-Im polyamides may be further explored as sensitizers to genotoxic therapies.
نوع الوثيقة: article
وصف الملف: electronic resource
اللغة: English
تدمد: 1932-6203
Relation: http://europepmc.org/articles/PMC5929528?pdf=render; https://doaj.org/toc/1932-6203
DOI: 10.1371/journal.pone.0196803
URL الوصول: https://doaj.org/article/a69e65bb62d345b58c3bae12d04a0bc8
رقم الانضمام: edsdoj.69e65bb62d345b58c3bae12d04a0bc8
قاعدة البيانات: Directory of Open Access Journals
الوصف
تدمد:19326203
DOI:10.1371/journal.pone.0196803