An Institute of Basic Sciences (IBS) research team has identified the principle that cancer suppressor protein ATAD5 regulates the termination of repairs on deoxyribonucleic acid (DNA) synthesis damaged by reactive oxygen.
Researchers revealed that ATAD5 protein regulates DNA synthesis and finishes repair at the DNA single-stranded cleavage caused by reactive oxygen species and maintains genome stability by reducing DNA nick exposure that causes the instability.
The IBS team, led by Researcher Lee Kyoo-young of the Center for Genomic Integrity, had previously found that ATAD5 protein relieves replication stress and helps stable DNA replication by controlling abnormal structures inside DNA.
Reactive oxygen species protect cells but can damage DNA when overproduced, leading to aging and cancer development. The human body responds to the damage by activating the DNA damage repair system. However, little has been revealed about the mechanism of repair DNA synthesis.
The research team first labeled the ATAD5 protein with a fluorescent protein and applied it to multiple DNA damages. As a result, the fluorescence signal of DNA-binding ATAD5 was increased specifically for reactive oxygen species.
The proliferating cell nuclear antigen (PCNA) gene, which aids in DNA synthesis, showed the same reaction.
The action indicates that PCNA binding becomes active when DNA is damaged by reactive oxygen species and increases ATAD5 activity. In addition, the study showed that single-strand break caused by reactive oxygen species to be the main type of damage leads to DNA synthesis.
The research team also found that ATAD5 plays a key role in DNA synthesis, the final step in DNA repair.
“We revealed a novel function of ATAD5 regulating repair of DNA damage caused by reactive oxygen species,” Lee said. “As reactive oxygen species are considered the main culprits of various diseases, including cancer and aging, we believe the findings to contribute to the development of cancer therapies and anti-aging agents in the future.”
The study results were published in the online edition of Nucleic Acids Research on Nov. 1.