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Original Research ARTICLE Provisionally accepted The full-text will be published soon. Notify me

Front. Cell. Neurosci. | doi: 10.3389/fncel.2019.00392

RAD6B Plays a Critical Role in Neuronal DNA Damage Response to Resist Neurodegeneration

Zhao Guo1, Yingxia Tian2, Yingli Guo1, Boya Li1, Xiangwen Liu1,  Kun Xie1, Yanfeng Song1* and  Degui Wang1*
  • 1School of Basic Medical Sciences, Lanzhou University, China
  • 2Gansu Provincial Cancer Hospital Gansu Provincial Academic Instiute for Medical Research, China

RAD6 participates in DNA double-strand breaks (DSBs) repair by ubiquitinating histone H2B in mitotic cells. In terminally differentiated cells, however, the mechanisms of DNA damage repair are less well known. In this study, we investigate whether RAD6B is involved in DSBs repair in neurons and effects of RAD6B deficiency on neuronal survival. We compared neurons of RAD6B-deficient mice with those of littermate wild type (WT) mice and induced DNA damage by X-ray irradiation. We provide evidence that RAD6B is essential for neural DDR and RAD6B deficiency results in increased genomic instability and neurodegeneration. Moreover, higher levels of p53 and p21 are present in the brains of RAD6B-deficient mice, which may be responsible for neuronal senescence and degeneration. In addition, behavioral experiments show that RAD6B-deficient mice exhibit marked learning and memory deficits. In conclusion, these findings suggest that RAD6B is critical for neural integrity and that the absence of RAD6B accelerates neurodegeneration in mice.

Keywords: Aging, Rad6B, Histone ubiquitination, senescence, Neurodegenaration, DNA Damage

Received: 10 Apr 2019; Accepted: 09 Aug 2019.

Edited by:

Rocío M. De Pablos, University of Seville, Spain

Reviewed by:

Fabrizio Palitti, Università degli Studi della Tuscia, Italy
Ray Truant, McMaster University, Canada  

Copyright: © 2019 Guo, Tian, Guo, Li, Liu, Xie, Song and Wang. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

* Correspondence:
Prof. Yanfeng Song, School of Basic Medical Sciences, Lanzhou University, Lanzhou, 730000, Gansu Province, China, songyanfeng@lzu.edu.cn
Mx. Degui Wang, School of Basic Medical Sciences, Lanzhou University, Lanzhou, 730000, Gansu Province, China, wangdegui@lzu.edu.cn