Details

Autor(en) / Beteiligte

• Diaz-Perez, Silvia
• Kane, Nathanael
• Kurmis, Alexis A
• Yang, Fei
• Kummer, Nicolas T
• Dervan, Peter B
• Nickols, Nicholas G
• Sobol, Robert W.

Titel

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

Ist Teil von

• PloS one, 2018-05, Vol.13 (5), p.e0196803

Ort / Verlag

United States: Public Library of Science

Erscheinungsjahr

2018

Quelle

MEDLINE

Beschreibungen/Notizen

• 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.