Triplex targeted genomic crosslinks enter separable deletion and base substitution pathways
| Autor: | Michael M. Seidman, Alokes Majumdar, Veronica Maher, Michel Bernier, Ji-Lan Liu, Sally Richards, Su-ting Liu, Rodney S. Nairn |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2005 |
| Předmět: |
Hypoxanthine Phosphoribosyltransferase
DNA Repair DNA repair Oligonucleotides macromolecular substances CHO Cells DNA-Directed DNA Polymerase Biology medicine.disease_cause Article chemistry.chemical_compound Cricetulus Cricetinae Genetics medicine Animals Humans Sequence Deletion Mutation Base Sequence Mutagenesis technology industry and agriculture Ficusin G1 Phase DNA Genomics Non-homologous end joining DNA-Binding Proteins Cross-Linking Reagents chemistry DNA mismatch repair ERCC1 Nucleotide excision repair |
| Zdroj: | Nucleic Acids Research |
| ISSN: | 1362-4962 0305-1048 |
| Popis: | We have synthesized triple helix forming oligonucleotides (TFOs) that target a psoralen (pso) interstrand crosslink to a specific chromosomal site in mammalian cells. Mutagenesis of the targeted crosslinks results in base substitutions and deletions. Identification of the gene products involved in mutation formation is important for developing practical applications of pso-TFOs, and may be informative about the metabolism of other interstrand crosslinks. We have studied mutagenesis of a pso-TFO genomic crosslink in repair proficient and deficient cells. Deficiencies in non homologous end joining and mismatch repair do not influence mutation patterns. In contrast, the frequency of base substitutions is dependent on the activity of ERCC1/XPF and polymerase zeta, but independent of other nucleotide excision repair (NER) or transcription coupled repair (TCR) genes. In NER/TCR deficient cells the frequency of deletions rises, indicating that in wild-type cells NER/TCR functions divert pso-TFO crosslinks from processes that result in deletions. We conclude that targeted pso-TFO crosslinks can enter genetically distinct mutational routes that resolve to base substitutions or deletions. |
| Databáze: | OpenAIRE |
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