Genetic Characterization of Three Distinct Mechanisms Supporting RNA-Driven DNA Repair and Modification Reveals Major Role of DNA Polymerase ζ
Autor: | Kuntal Mukherjee, Chance Meers, Alli L. Gombolay, Francesca Storici, Gabor Banyai, Gary P. Newnam, Havva Keskin, Efiyenia I. Kaparos, Olga M. Mazina, Taehwan Yang, Alexander V. Mazin |
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Rok vydání: | 2019 |
Předmět: |
Adult
DNA Replication DNA Complementary Adolescent DNA Repair DNA polymerase DNA repair DNA-Directed DNA Polymerase Saccharomyces cerevisiae Genomic Instability Article 03 medical and health sciences chemistry.chemical_compound Young Adult 0302 clinical medicine Homologous chromosome Humans A-DNA DNA Breaks Double-Stranded Molecular Biology 030304 developmental biology 0303 health sciences biology RNA Cell Biology DNA Middle Aged Reverse transcriptase Cell biology Rad52 DNA Repair and Recombination Protein chemistry biology.protein Homologous recombination 030217 neurology & neurosurgery |
Zdroj: | Mol Cell |
ISSN: | 1097-4164 |
Popis: | DNA double-stranded breaks (DSBs) are dangerous lesions threatening genomic stability. Fidelity of DSB repair is best achieved by recombination with a homologous template sequence. In yeast, transcript RNA was shown to template DSB repair of DNA. However, molecular pathways of RNA-driven repair processes remain obscure. Utilizing assays of RNA-DNA recombination with and without an induced DSB in yeast DNA, we characterize three forms of RNA-mediated genomic modifications: RNA- and cDNA-templated DSB repair (R-TDR and c-TDR) using an RNA transcript or a DNA copy of the RNA transcript for DSB repair, respectively, and a new mechanism of RNA-templated DNA modification (R-TDM) induced by spontaneous or mutagen-induced breaks. While c-TDR requires reverse transcriptase, translesion DNA polymerase ζ (Pol ζ) plays a major role in R-TDR, and it is essential for R-TDM. This study characterizes mechanisms of RNA-DNA recombination, uncovering a role of Pol ζ in transferring genetic information from transcript RNA to DNA. |
Databáze: | OpenAIRE |
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