Molecular Cell
Volume 79, Issue 6, 17 September 2020, Pages 1037-1050.e5
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Article
Genetic Characterization of Three Distinct Mechanisms Supporting RNA-Driven DNA Repair and Modification Reveals Major Role of DNA Polymerase ζ

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Highlights

  • DNA polymerase ζ promotes RNA-templated DNA repair and modification

  • cDNA-, unlike RNA-templated DNA repair, requires end-clipping function

  • RNA-mediated DNA modification proceeds in the absence of recombination genes

  • Mismatch repair facilitates accurate repair with template RNA

Summary

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.

Keywords

DNA repair
RNA-mediated
RNA-templated
homologous recombination
reverse transcriptase
cDNA-mediated
translesion polymerase
DNA polymerase ζ
REV3
RNA recombination

Cited by (0)

3

Present address: Department of Biochemistry and Molecular Biophysics, Columbia University, New York, NY 10032, USA

4

Present address: Omega Bio-Tek, Norcross, GA 30071, USA

5

Present address: School of Medicine, New York University, New York, NY 10016, USA

6

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