Human Mitochondrial Protein HSPD1 Binds to and Regulates the Repair of Deoxyinosine in DNA

The generation of deoxyinosine (dI) in DNA is one of the most important sources of genetic mutations, which may lead to cancer and other human diseases. A further understanding of the biological consequences of dI necessitates the identification and functional characterizations of dI-binding proteins. Herein, we employed a mass spectrometry-based proteomics approach to detect the cellular proteins that may sense the presence of dI in DNA. Our results demonstrated that human mitochondrial heat shock protein 60 (HSPD1) can interact with dI-bearing DNA. We further demonstrated the involvement of HSPD1 in the sodium nitrite-induced DNA damage response and in the modulation of dI levels in vitro and in human cells. Together, these findings revealed HSPD1 as a novel dI-binding protein that may play an important role in the mitochondrial DNA damage control in human cells.