New progress in DNA repair and tumor regulation mechanisms

New progress in DNA repair and tumor regulation mechanisms

December 19, 2018 Source: Ministry of Science and Technology

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Under the support of the national key research and development plan “Protein machinery and life process regulation” key project “The functional mechanism of protein machinery in the process of infection and pathogenesis of important pathogens”, the Gebao team of Tongji University and Mao Zhiyong team cooperated to discover DNA repair. New mechanisms for tumor regulation.

Genomic DNA faces a variety of injuries, and damage that cannot be repaired in time can lead to tumors. Cyclic guanylate-adenylate synthetase (cGAS) is a DNA recognition receptor that recognizes pathogenic microorganisms and self-DNA in the human cytoplasm and activates immune responses. The physiological process of cGAS is only studied in the cytoplasm, and it is not clear whether it enters the nucleus directly involved in DNA damage repair.

The team first discovered that cGAS can transfer from the cytoplasm to the nucleus after DNA damage, and one of the main repair methods to inhibit DNA double-strand break repair - homologous recombination repair, leading to genomic instability, and ultimately promote tumorigenesis And development. This study, for the first time, systematically elucidates the new functions of cGAS in the nucleus completely independent of DNA recognition function. It not only promotes the functional research of cGAS to a new field, but also finds an important target in the development of anti-tumor drugs. The theoretical basis for the development of new anti-tumor drugs based on the intervention of cGAS into the nucleus. Related results were recently published in the journal Nature.

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