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conferenceseries
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Volume 5, Issue 2 (Suppl)
Transcriptomics, an open access journal
ISSN: 2329-8936
Molecular Biology 2017
August 31-September 01, 2017
2
nd
International Conference on
August 31-September 01, 2017 Philadelphia, USA
Molecular Biology, Nucleic Acids &
Molecular Medicine
RNA-templated DNAdouble-strand break repair: Role of RAD52
Alexander V Mazin
Drexel University College of Medicine, USA
Statement of the Problem:
Homologous recombination (HR) is a high-fidelity process that uses homologous DNA sequences
as a template to repair damaged DNA. However, we recently demonstrated that transcript RNA can also serve as template for
DSB repair via HR in yeast. Currently, little is known about the enzymatic machinery that executes RNA-templated DSB repair.
Our results from budding yeast implicated Rad52 in this RNA-directed DSB repair mechanism. However, the exact mechanism
of how RAD52 contributes to RNA-dependent DSB repair remains to be elucidated.
Methodology &Theoretical Orientation:
Using biochemical and genetic approaches in yeast we investigate this mechanism.
Findings:
We found that RAD52 carries inverse strand exchange activity between homologous dsDNA and ssRNA, which
could account for the role of RAD52 in RNA-dependent DNA repair identified in our genetic experiments. This activity is
distinct from canonical “forward” DNA strand exchange which is carried by the major recombinase RAD51 between ssDNA
and homologous dsDNA. We demonstrate that both human and yeast RAD52 efficiently promotes inverse strand exchange
between dsDNA and homologous ssRNA or ssDNA. We show that in eukaryotes, inverse RNA strand exchange is a distinctive
activity of RAD52; neither the major recombinase RAD51, nor the yeast RAD59 carries this activity. Our genetic experiments
in yeast support the biological significance of inverse RNA strand exchange.
Conclusion & Significance:
It was demonstrated that RAD52 inactivation causes synthetic lethality in combination with
mutations in BRCA1 and BRCA2 proteins, defects of which are associated with various types of cancer. These data indicated
an essential back-up function of RAD52, which may complement the BRCA-dependency in humans. We suggest that the novel
RAD52 inverse strand exchange activities contribute to this back-up function. Thus, our findings may help to identify new
therapeutic targets for cancer.
amazin@drexelmed.eduTranscriptomics 2017, 5:2 (Suppl)
DOI: 10.4172/2329-8936-C1-013