News Releases & Research Results Elucidation of the genetic mechanism of efficient DNA damage repair - Revelation of the pathogenesis of Cockayne syndrome (progeria), a rare hereditary intractable disease/Establishment of a disease mouse model useful for elucidating the pathological conditions of various aging-related symptoms and developing therapeutic drugs -

The results of research and development conducted by Professor Tomoo Ogi and Assistant Professor Yuka Nakazawa of the Department of Genetics, Research Institute of Environmental Medicine, Nagoya University.

• "RNA synthetase," a protein complex for ribonucleic acid (RNA) transcription, was demonstrated to be recognized with a specific marker (ubiquitination*) for efficient DNA damage repair during gene transcription.
  * A small protein called "ubiquitin," consisting of 76 amino acids, binds to lysine residues in other proteins to promote their degradation and functional activation.
• A mouse model was created by inhibiting the ubiquitination of RNA synthetase, showing various aging-related symptoms, such as neurological symptoms similar to those of human hereditary progeria such as Cockayne syndrome.
• The results of R&D should contribute to the elucidation of the pathological conditions of various aging-related human diseases and the development of therapeutic drugs, as well as basic research on transcription.

This R&D project was conducted with the support of Practical Research Project for Rare/Intractable Diseases by AMED.

The results of R&D were published online in the American scientific journal, Cell, on March 6.

Nakazawa Y., et al. Ubiquitination of DNA damage-stalled RNAPII promotes transcription-coupled repair Cell
DOI：10.1016/j.cell.2020.02.010