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Interference with DNA repair after ionizing radiation by a pyrrole-imidazole polyamide.
Diaz-Perez, Silvia; Kane, Nathanael; Kurmis, Alexis A; Yang, Fei; Kummer, Nicolas T; Dervan, Peter B; Nickols, Nicholas G.
Afiliación
  • Diaz-Perez S; Department of Radiation Oncology, University of California, Los Angeles, California, United States of America.
  • Kane N; Department of Radiation Oncology, University of California, Los Angeles, California, United States of America.
  • Kurmis AA; Division of Chemistry and Chemical Engineering, California Institute of Technology, Pasadena, California, United States of America.
  • Yang F; Division of Chemistry and Chemical Engineering, California Institute of Technology, Pasadena, California, United States of America.
  • Kummer NT; Department of Radiation Oncology, University of California, Los Angeles, California, United States of America.
  • Dervan PB; Division of Chemistry and Chemical Engineering, California Institute of Technology, Pasadena, California, United States of America.
  • Nickols NG; Department of Radiation Oncology, University of California, Los Angeles, California, United States of America.
PLoS One ; 13(5): e0196803, 2018.
Article en En | MEDLINE | ID: mdl-29715291
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.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Pirroles / ADN / Reparación del ADN / Imidazoles / Nylons Límite: Humans Idioma: En Revista: PLoS One Asunto de la revista: CIENCIA / MEDICINA Año: 2018 Tipo del documento: Article País de afiliación: Estados Unidos Pais de publicación: Estados Unidos
Texto completo
Añadir a Mi BVS
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XML
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Pirroles / ADN / Reparación del ADN / Imidazoles / Nylons Límite: Humans Idioma: En Revista: PLoS One Asunto de la revista: CIENCIA / MEDICINA Año: 2018 Tipo del documento: Article País de afiliación: Estados Unidos Pais de publicación: Estados Unidos