PhD Oral Defense: DNA double-strand breaks in early developing embryos: occurrence, consequences and regulation of repair mechanisms

PhD Oral Defense of Rodrigo Camponogara Bohrer, Department of Animal Science

DNA DSBs are the most important type of DNA damage because their defective repair can induce genome instability, deleterious mutations and cellular death. Studies, most using mice and humans, have shown that DNA DSBs is an important component affecting early embryo development and somatic cell reprogramming during the production of iPS cells. However, the occurrence and effects of DNA DSBs, and the mechanism involved in DNA DSBs repair have not been systematically investigated during early embryo development and cell reprogramming in embryos produced by somatic cell nuclear transfer (SCNT). Therefore, in the first manuscript of this thesis, we characterized the occurrence of DNA DSBs during early development of IVF and SCNT porcine embryos. ... In the second manuscript of this thesis, we investigated the effect of HDACi treatment on DNA DSBs repair and development of SCNT embryos.  ... In the third manuscript, we compared the occurrence of DSBs between early- and late-cleaving embryos. Our results showed that the presence of DNA DSBs affects the cleavage kinetics and embryo developmental capacity to the blastocyst stage. Finally, in the fourth manuscript of this thesis, we assessed the importance of the HR and the NHEJ pathways for DNA DSBs repair during early embryo development.

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