Nature: Tongji University finds cGAS enzymes at risk of cancer
October 26, 2018 Source: Science Network
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Professor Ge Baoxue from Tongji University School of Medicine, Tongji University Affiliated Pulmonary Hospital, Professor Mao Zhiyong from the College of Life Science and Technology of Tongji University and the First Maternal and Child Health Hospital affiliated to Tongji University for the first time systematically explained that cGAS is completely independent of DNA recognition. The new function in the nucleus provides a theoretical basis for the development of new anti-tumor drugs based on the intervention of cGAS into the nucleus. On October 25th, this important research was published online in Nature.
This morning, Nature magazine sent a message to the research team that the paper will be featured in the internationally renowned academic journal Nature Reviews Molecular Cell Biology.
cGAS, called avian adenosine synthase, is a DNA recognition receptor. It was first identified by Professor Chen Zhijian, a famous Chinese scholar in the United States, and has a milestone in the field of DNA recognition and innate immunity. This synthetase promotes the production of type I interferons and immune factors.
During normal growth and metabolism, cells are affected by various internal and external factors, and DNA is always damaged by different forms. DNA double-strand breaks are the most serious form of DNA damage. It can not be repaired or repaired by mistakes, which will lead to increased genomic instability, which will lead to chromosome rearrangement and loss of genetic information. Bring cells into apoptosis, aging and even lead to tumors.
The researchers found that cGAS translocates into the nucleus of cells when DNA damage occurs, and is recruited to the site of DNA damage, by interfering with the formation of PAPR1/Timeless complex, inhibiting DNA double-strand break damage repair, thereby increasing the genome. The instability and ultimately increased the risk of tumor formation. The study also found that cGAS inhibits DNA repair by a pathway that is completely independent of its DNA recognition function.
"cGAS will inhibit DNA repair and promote tumor formation. This is the first time we have discovered a new function of cGAS in the world." Gebao said that the previous understanding of cGAS is focused on innate immunity, that is, cGAS as A DNA receptor that recognizes pathogenic microorganisms and self-DNA in the human cytoplasm and activates the immune response. The study of its physiological processes is only in the cytoplasm. However, the cancer-promoting function of cGAS was first discovered, so this achievement will push the functional research of cGAS into a new field.
This important finding laid the theoretical foundation for the development of new anti-tumor drugs. “CGAS is like a demon in a bottle.†Ge Baoxue said that “into nuclear†is a key point. If we can intervene in cGAS and keep it “closed†in the cytoplasm, it will not 闯Going into the "nucleus" to do bad things. This will become an important target in the development of anti-tumor drugs.
"To do research, we must broaden our thinking and vision. There are two aspects of yin and yang. We hope that our discovery will provide researchers with some research ideas and innovative inspirations," said Professor Ge Baoxue.
Professor Ge Baoxue and Professor Mao Zhiyong are the co-authors of this article. Liu Haipeng, associate researcher of the affiliated pulmonary hospital of Tongji University, Zhang Haiping, Ph.D. student of Tongji University, and Wu Xiangyang, a doctoral student of Tongji University School of Medicine, are the co-first authors of this article. This research work was funded by the Ministry of Science and Technology, the National Natural Science Foundation of China, and the Shanghai Municipal Science and Technology Commission. It was also supported by research teams such as Fudan University, Xiangya Medical College, and Max Planck Institute for Infectious Biology.
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