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Accepted (AM)Open Access (License Unspecified), Open
Journal article
Transcript-RNA-templated DNA recombination and repair
Nature (London), v 515(7527), pp 436-439
20 Nov 2014
PMID: 25186730
Featured in Collection : UN Sustainable Development Goals @ Drexel
Abstract
Homologous recombination is a molecular process that has multiple important roles in DNA metabolism, both for DNA repair and genetic variation in all forms of life. Generally, homologous recombination involves the exchange of genetic information between two identical or nearly identical DNA molecules; however, homologous recombination can also occur between RNA molecules, as shown for RNA viruses. Previous research showed that synthetic RNA oligonucleotides can act as templates for DNA double-strand break (DSB) repair in yeast and human cells, and artificial long RNA templates injected in ciliate cells can guide genomic rearrangements. Here we report that endogenous transcript RNA mediates homologous recombination with chromosomal DNA in yeast Saccharomyces cerevisiae. We developed a system to detect the events of homologous recombination initiated by transcript RNA following the repair of a chromosomal DSB occurring either in a homologous but remote locus, or in the same transcript-generating locus in reverse-transcription-defective yeast strains. We found that RNA-DNA recombination is blocked by ribonucleases H1 and H2. In the presence of H-type ribonucleases, DSB repair proceeds through a complementary DNA intermediate, whereas in their absence, it proceeds directly through RNA. The proximity of the transcript to its chromosomal DNA partner in the same locus facilitates Rad52-driven homologous recombination during DSB repair. We demonstrate that yeast and human Rad52 proteins efficiently catalyse annealing of RNA to a DSB-like DNA end in vitro. Our results reveal a novel mechanism of homologous recombination and DNA repair in which transcript RNA is used as a template for DSB repair. Thus, considering the abundance of RNA transcripts in cells, RNA may have a marked impact on genomic stability and plasticity.
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Details
- Title
- Transcript-RNA-templated DNA recombination and repair
- Creators
- Havva Keskin - Georgia Institute of TechnologyYing Shen - Georgia Institute of TechnologyFei Huang - Drexel UniversityMikir Patel - Drexel UniversityTaehwan Yang - Georgia Institute of TechnologyKatie Ashley - Georgia Institute of TechnologyAlexander V Mazin - Drexel UniversityFrancesca Storici - Georgia Institute of Technology
- Publication Details
- Nature (London), v 515(7527), pp 436-439
- Publisher
- Springer Nature
- Grant note
- R56 CA100839 / NCI NIH HHS CA100839 / NCI NIH HHS P30CA056036 / NCI NIH HHS R01 CA100839 / NCI NIH HHS P30 CA056036 / NCI NIH HHS
- Resource Type
- Journal article
- Language
- English
- Academic Unit
- Biochemistry and Molecular Biology
- Web of Science ID
- WOS:000345770600051
- Scopus ID
- 2-s2.0-84911500734
- Other Identifier
- 991019167758004721
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- Collaboration types
- Domestic collaboration
- Web of Science research areas
- Biochemistry & Molecular Biology