News Release

Key regulating protein found in homologous recombination and cell survival

Peer-Reviewed Publication

Hefei Institutes of Physical Science, Chinese Academy of Sciences

Key Regulating Protain Found in Homologous Recombination and Cell Survival

image: Schematic illustration of the mechanism of HIGD1A regulating HR view more 

Credit: CHEN Bin

According to a research published in Oncogene recently, a team led by Prof. Zhao Guoping from Hefei Institutes of Physical Science (HFIPS), Chinese Academy of Sciences (CAS) found, for the first time, that IR induced the translocation of mitochondrial HIGD1A, an important mitochondrial protein, to the nucleus, and promoted HR and radio-resistance.  

This is of great significance for analyzing the role of mitochondrial in radiation sensitivity, and the development of new radiosensitizers.

Radiation-induced DNA damage response is the theoretical basis of radiotherapy, and how to improve the sensitivity of tumors to radiation is the key factor in clinical radiotherapy. Mitochondria are among the vital cell organelles that are tightly integrated and show cellular responses to various stressors, including DNA damage. Recent studies have found that the mitochondrial factor HIGD1A translocates from the mitochondria to the nucleus under severe stress, suggesting that it may play critical extramitochondrial moonlighting roles in the DNA damage repair pathway, but the specific mechanism is not clear.

In this study, by using bioinformatics analysis, RNA-seq, LC-MS/MS and other techniques, researchers found that DNA damage-induced translocation of mitochondrial factor HIGD1A into the nucleus regulates homologous recombination and affects sensitivity to radiation therapeutics in multiple tumor cell lines. This study demonstrated a novel regulatory role of HIGD1A in DNA damage repair through dynamically regulating RPA1-ssDNA binding and timely removing RPA1 from DSBs sites. In addition, clinical inhibitor, and in vivo studies confirmed the radio-sensitizing effect of HIGD1A.
Collectively, these results provide convincing evidence that HIGD1A serves as a promising target to sensitize cancer to radio-therapy.

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