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DNA Polymerase ζ Drives RNA-DNA Recombination

90 Pages Posted: 14 Jan 2020 Sneak Peek Status: Under Review

See all articles by Chance Meers

Chance Meers

Georgia Institute of Technology - School of Biological Sciences

Havva Keskin

Georgia Institute of Technology - School of Biological Sciences

Gabor Banyai

Georgia Institute of Technology - School of Biological Sciences

Olga Mazina

Drexel University - Department of Biochemistry and Molecular Biology

Taehwan Yang

Georgia Institute of Technology - School of Biological Sciences

Alli L. Gombolay

Georgia Institute of Technology - School of Biological Sciences

Efiyenia I. Kaparos

Georgia Institute of Technology - School of Biological Sciences

Gary Newnam

Georgia Institute of Technology - School of Biological Sciences

Alexander Mazin

Drexel University - Department of Biochemistry and Molecular Biology

Francesca Storici

Georgia Institute of Technology - School of Biological Sciences

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Abstract

DNA double-strand 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 chromosomal 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 reveal a major role of translesion DNA polymerase ζ in DSB repair by RNA. Moreover, Pol ζ catalytic subunit Rev3 with Rev1 and Rad5 are essential for RNA-templated DNA modification with no DSB. Contrary to RNA-templated DNA repair and modification, DSB repair templated by RNA copied into DNA (cDNA) is dependent on the reverse transcriptase activity of the yeast retrotransposon, and clippases Rad1-10/Msh2-3. This study characterizes mechanisms of RNA-DNA recombination, uncovering a new role of Pol ζ in transferring genetic information from RNA to DNA.

Keywords: DNA repair, DSB repair, RNA-mediated, RNA-templated, homologous recombination, reverse transcriptase, cDNA-mediated, Ty-less, translesion polymerase, DNA polymerase Zeta, REV3, REV1, RAD5, RAD1, RAD10, MSH2, MSH3, RNA recombination.

Suggested Citation

Meers, Chance and Keskin, Havva and Banyai, Gabor and Mazina, Olga and Yang, Taehwan and Gombolay, Alli L. and Kaparos, Efiyenia I. and Newnam, Gary and Mazin, Alexander and Storici, Francesca, DNA Polymerase ζ Drives RNA-DNA Recombination. MOLECULAR-CELL-D-19-02370. Available at SSRN: https://ssrn.com/abstract=3517554 or http://dx.doi.org/10.2139/ssrn.3517554
This is a paper under consideration at Cell Press and has not been peer-reviewed.

Chance Meers (Contact Author)

Georgia Institute of Technology - School of Biological Sciences ( email )

Atlanta, GA 30332
United States

Havva Keskin

Georgia Institute of Technology - School of Biological Sciences

Atlanta, GA 30332
United States

Gabor Banyai

Georgia Institute of Technology - School of Biological Sciences

Atlanta, GA 30332
United States

Olga Mazina

Drexel University - Department of Biochemistry and Molecular Biology

United States

Taehwan Yang

Georgia Institute of Technology - School of Biological Sciences

Atlanta, GA 30332
United States

Alli L. Gombolay

Georgia Institute of Technology - School of Biological Sciences

Atlanta, GA 30332
United States

Efiyenia I. Kaparos

Georgia Institute of Technology - School of Biological Sciences

Atlanta, GA 30332
United States

Gary Newnam

Georgia Institute of Technology - School of Biological Sciences

Atlanta, GA 30332
United States

Alexander Mazin

Drexel University - Department of Biochemistry and Molecular Biology

United States

Francesca Storici

Georgia Institute of Technology - School of Biological Sciences

Atlanta, GA 30332
United States

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