Professor Kaoru Sugazawa of the Center for Advanced Fusion Research, Kobe University, has collaborated with Friedrich-Mischer Institute for Biological Medicine (Switzerland) and others to explain how UV-damaged DNA is repaired at the molecular level. I revealed it for the first time in.The results of this research are published in the British scientific journal "Nature".
DNA damage is said to occur more than tens of thousands of times per cell even in a day, and if repair cannot keep up, DNA replication and transcription are hindered, causing cell death and chromosomal instability, leading to canceration. There is also a risk of connection.Therefore, smooth DNA repair is essential for cells to function and survive normally.
Ultraviolet rays are one of the causes of DNA damage.When DNA is damaged by UV rays, it is important for repair that the protein complex "CRL4ADDB2 ubiquitin ligase" finds the damage and binds to it, causing a phenomenon called ubiquitination.On the other hand, when DNA does not need to be repaired, ubiquitination is suppressed by another protein complex called "COP9 signarosome (CSN)".However, it was unclear how the control of ubiquitination, which is important in this repair mechanism, is performed.
The research team analyzed the three-dimensional structure of CRL4ADDB2 ubiquitin ligase using a cryo-electron microscope.We have clarified the mechanism by which the protein NEDD8, which acts as a "switch," binds to activate the protein and initiate DNA repair.It was also clarified that when there is no need for further repair, CSN binds to CRL4ADDB2 ubiquitin ligase, causing structural changes and removing NEDD8, which acts as a switch.This mechanism is important for maintaining the DNA repair activity of cells because the CRL4ADDB2 ubiquitin ligase itself is degraded by ubiquitination if not controlled.
"The regulatory mechanism clarified at the molecular level this time is universal," the research team said, aiming to apply it to drug discovery that leads to suppression of skin cancer, including DNA repair, in the future. is.