Professor Kaoru Sugazawa of the Research Center for Biosignals, Kobe University, Professor Hitoshi Kurumizaka of the Institute of Quantitative Life Sciences, the University of Tokyo, and Professor Shigenori Iwai of the Graduate School of Osaka University have efficiently detected and repaired DNA damage caused by ultraviolet rays. Clarified the mechanism.

 Damage to genomic DNA, which is said to occur more than tens of thousands of times per cell per day, causes inhibition of DNA replication and transcription, cell death and chromosomal instability when repair is not in time, and even cells There is also a risk of becoming cancerous.

 When DNA is damaged by ultraviolet light, which is one of the factors that cause DNA damage, a protein complex called UV-DDB finds the damage and binds to it to initiate repair.However, because DNA wraps around histone proteins to form structures called "nucleosomes," UV-DDB damage depends on whether the DNA damage is exposed or hidden inside the nucleosome. Access is expected to be affected.

 In order to investigate how UV-DDB efficiently detects damage, the three-dimensional structure of the complex in which nucleosomes are formed by DNA containing damage and histone proteins at specific positions and UV-DDB is bound to this is formed. Analyzed.As a result, when the damage is exposed outside the nucleosome, UV-DDB binds to the damage with little change in the structure of the original nucleosome, while the damage is hidden inside the nucleosome. Surprisingly, the DNA double helix "slides" a few bases along the surface of the histone protein, causing the damage to move outward from the beginning and bind UV-DDB.

 The mechanism by which UV-DDB causes structural changes in nucleosomes to enable the initiation of repair reactions has been elucidated, and if its artificial control becomes possible, it will protect against UV rays and prevent skin cancer. There is a possibility that it can be applied to connected drug discovery.

Paper information:[Nature] DNA damage detection in nucleosomes involves DNA register shifting

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