肿瘤基因组稳定性 z-bo 2020-09-21 358

　　Chromosomal DNA replication, DNA damage response and repair are one of the most basic life phenomena to ensure the stability of the life genome. The groundbreaking research on DNA repair mechanism won the 2015 Nobel Prize in Chemistry. The complete cell division cycle is divided into pre-replication (G1), DNA replication (S), late-stage replication (G2) and thread division (M).

　　Academic circles believe that DNA replication only occurs in the S phase of the cell cycle. Normal cell division follows the classic cell division cycle theory, and DNA replication is completed in S phase. In tumor cells, oncogenes can induce DNA replication pressure, but due to the presence of DNA replication pressure in overgrown tumor cells, DNA replication in the "predetermined action" stage S will cause a lot of DNA damage. It left behind and greatly degraded the DNA. Stability leads to the instability of tumor cell genome, which is also an important driving factor for cancer. At the same time, tumor cells may need some special repair mechanisms to maintain the stability of tumor cell genes to meet the needs of survival and rapid growth. In a joint study conducted by Zhejiang University School of Medicine and the University of Copenhagen in Denmark, lung cancer cells also showed DNA replication behavior during online division (M phase), and the copied DNA mainly identified "vulnerable sites in the genome" ". Was found in. In the early stage of online division, lung cancer cells rely on nuclease MUS81 and DNA polymerase POLD3 to initiate DNA replication, thereby reducing false unseparated chromosomes. Therefore, in the final stage of the cell cycle, DNA replication is used to repair DNA damage caused by replication pressure in tumor cells and maintain chromosomal stability. Previous studies have shown that fragile sites on chromosomes appear as gaps or discontinuous spacers during cell division. The fragile sites between species are conserved, and the chromosomes in this region are prone to damage, and it is speculated that it will affect the pseudogenome rearrangement associated with tumors.

　　This study re-examined the mechanisms in vulnerable areas. The vulnerable part is not the actual chromosome break, but the newly synthesized DNA region during cell division. The reason it looks like it is broken is that the newly synthesized DNA region is not tightly connected to the rest of the chromosome. Lung cancer cells use this special period of DNA replication mode to achieve unlimited malignant growth. This study is the first breakthrough in discovering that lung cancer cells have DNA replication during mitosis, which allows tumor cells to maintain genome stability. This is an important mechanism. Professor Ian D. Hixon, a scholar of the Royal Academy of Sciences, pointed out that the discovery of DNA replication during line division is of great significance to many fields, including nucleic acid repair, replication and tumor research. In recent years, the incidence of lung cancer and other malignant tumors has increased. The specific signaling pathways that lung cancer cells found in this study rely on mitotic DNA replication of lung cancer cells provide new potential therapeutic targets for lung cancer targeted therapy.