The mechanism of how proteins terminate the chromosomal replication and repair processes has been discovered.
Researchers of the Institute for Basic Science (IBS) announced on June 3 that they have identified the mechanism by which the proliferating cell nuclear antigen (PCNA) bound to DNA is separated by the ATAD5-RLC protein after chromosomal replication.
This study was carried out by a team led by principal investigator Kang Seok-hyun of the IBS Center for Genomic Integrity and a team led by professor Kim Ha-jin of the Ulsan Institute of Science and Technology (UNIST). The IBS said that this study is important in that it has identified the control mechanism that prevents alteration of genetic information by ensuring that the chromosomal replication process and damage repair process are normally terminated.
Chromosomal replication is initiated by the DNA binding of proteins involved in DNA production. Of these proteins, PCNA, a ring-shaped protein, binds to DNA in a thread in needle form, leading the chromosome replication and repair. At the end of this process, PCNA separates from DNA, and chromosome replication is terminated. This study has revealed the principle of how PCNA breaks away from DNA.
The team devised an experimental method to track the binding and separation of PCNA and DNA and a monomolecular fluorescence imaging experiment to observe binding and separation in real time. As a result, they revealed the biochemical mechanism of terminating chromosomal replication by ATAD5-RLC protein, which cleaves the closed loop of PCNA and separates it from the DNA. In addition, the team identified the structural properties of ATAD5-RLC required for the isolation of PCNA. The researchers found that the ATAD5-RLC protein is involved in termination of normal chromosomal replication as well as the termination of chromosomal repair by separating PCNA modified by chromosomal damage from DNA.
Myung Kyung-jae, head of Center for Genomic Integrity, said, "If chromosomal replication is not terminated correctly, diseases such as cancer can occur. In that sense, this study will contribute to the identification of the foundational cause of abnormalities in genetic information and to the development of ultimate treatments."
The results of this study were published in the online edition of Nature Communications on June 3.