Although cancer cells divide at a significantly faster pace than do normal cells, their genetic quality is relatively stable. Research teams led by Prof. Ian D. Hickson of the University of Copenhagen and Prof. Shen Huahao of the Second Affiliated Hospital and the State Key Laboratory of Respiratory Disease, Zhejiang University, collaborate with each other to discover replication stress which activates DNA repair synthesis in mitosis. Their research findings, published online in Nature, are of appreciable theoretical and practical significance.
The classic theory of cell division concludes that a complete cell cycle consists of four discrete stages: the pre-duplication phase (G1), the DNA synthesis phase (S), the post-duplication phase (G2) and the mitosis phase (M). It is generally accepted that the duplication of DNA can only take place in the S phase of the cell cycle.
“We detect a very intriguing phenomenon in tumor genes,” said Ying Songmin, one of the first co-authors and a professor of the School of Medicine, Zhejiang University, “Normal cells complete their DNA duplication in the S phase, but tumor cells have another mechanism. They are duplicated very quickly in the S phase, thus doing much damage to the DNA and making it very erratic. They are thus more vulnerable to injuries.” Researchers first discover that the genomic DNA is also duplicated in cancer cells in the M phase.
“We also find that duplication of the genomic DNA in the M phase is unique to tumor cells and that it plays an extremely crucial role in maintaining the genetic stability of tumor cells”, said Ying Songmin.
Ian Hickson pointed out that discovering the duplication of the genomic DNA will produce a far-reaching impact on various fields, including DNA repair, DNA duplication and cancer. Prof. Liu Ying of the University of Copenhagen stressed that this research is ground-breaking in that it resolves a scientific puzzle in this field. “The POLD3-dependent mitotic DNA synthesis is enhanced in cancer cells that exhibit intrinsically high levels of chromosomal instability (CIN+) and replicative stress. Therefore, targeting this pathway could represent a new therapeutic approach,” said Shen Huahao.
On the basis of this research, the State Key Laboratory of Respiratory Disease of Zhejiang University is currently carrying out several research projects so as to gain a more insightful understanding of the molecular mechanism for DNA repair and its regulatory role in chronic airway inflammation and lung cancer.
