BRCA1 Promotes Repair of DNA Damage in Cochlear Hair Cells and Prevents Hearing Loss.
Weitao Jiang, Guanrun Wang, Feng Bai, Bing Hu, Yang Xu, Xingzhi Xu, Guohui Nie, Wei-Guo Zhu, Fangyi Chen, Xin-Hai Pei
Author Information
Weitao Jiang: International Cancer Center, Marshall Laboratory of Biomedical Engineering, Department of Otolaryngology, The First Affiliated Hospital, Department of Anatomy and Histology, Shenzhen University Medical School, Shenzhen 518060, China. ORCID
Guanrun Wang: International Cancer Center, Marshall Laboratory of Biomedical Engineering, Department of Otolaryngology, The First Affiliated Hospital, Department of Anatomy and Histology, Shenzhen University Medical School, Shenzhen 518060, China.
Feng Bai: Department of Pathology, Shenzhen University Medical School, Shenzhen 518060, China.
Bing Hu: Shenzhen Key Laboratory of Nanozymes and Translational Cancer Research, Department of Otolaryngology, Shenzhen Institute of Translational Medicine, The First Affiliated Hospital of Shenzhen University, Shenzhen Second People's Hospital, Shenzhen 518035, China.
Yang Xu: Department of Biomedical Engineering, Southern University of Science and Technology, Shenzhen 518055, China. ORCID
Xingzhi Xu: Guangdong Key Laboratory for Genome Stability & Disease Prevention and International Cancer Center, Shenzhen University Medical School, Shenzhen, 518060, China.
Guohui Nie: Shenzhen Key Laboratory of Nanozymes and Translational Cancer Research, Department of Otolaryngology, Shenzhen Institute of Translational Medicine, The First Affiliated Hospital of Shenzhen University, Shenzhen Second People's Hospital, Shenzhen 518035, China.
Wei-Guo Zhu: Department of Biochemistry and Molecular Biology, International Cancer Center, Shenzhen University Medical School, Shenzhen 518060, China.
Fangyi Chen: Department of Biomedical Engineering, Southern University of Science and Technology, Shenzhen 518055, China.
Xin-Hai Pei: International Cancer Center, Marshall Laboratory of Biomedical Engineering, Department of Otolaryngology, The First Affiliated Hospital, Department of Anatomy and Histology, Shenzhen University Medical School, Shenzhen 518060, China peixinhai@szu.edu.cn. ORCID
Cochlear hair cells (HCs) sense sound waves and allow us to hear. Loss of HCs will cause irreversible sensorineural hearing loss. It is well known that DNA damage repair plays a critical role in protecting cells in many organs. However, how HCs respond to DNA damage and how defective DNA damage repair contributes to hearing loss remain elusive. In this study, we showed that cisplatin induced DNA damage in outer hair cells (OHCs) and promoted OHC loss, leading to hearing loss in mice of either sex. Cisplatin induced the expression of Brca1, a DNA damage repair factor, in OHCs. Deficiency of Brca1 induced OHC and hearing loss, and further promoted cisplatin-induced DNA damage in OHCs, accelerating OHC loss. This study provides the first in vivo evidence demonstrating that cisplatin mainly induces DNA damage in OHCs and that BRCA1 promotes repair of DNA damage in OHCs and prevents hearing loss. Our findings not only demonstrate that DNA damage-inducing agent generates DNA damage in postmitotic HCs but also suggest that DNA repair factors, like BRCA1, protect postmitotic HCs from DNA damage-induced cell death and hearing loss.
