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3 March 2017 Autophagy Promotes the Repair of Radiation-Induced DNA Damage in Bone Marrow Hematopoietic Cells via Enhanced STAT3 Signaling
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Abstract

Autophagy protects hematopoietic cells from radiation damage in part by promoting DNA damage repair. However, the molecular mechanisms by which autophagy regulates DNA damage repair remain largely elusive. Here, we report that this radioprotective effect of autophagy depends on STAT3 signaling in murine bone marrow mononuclear cells (BM-MNCs). Specifically, we found that STAT3 activation and nuclear translocation in BM-MNCs were increased by activation of autophagy with an mTOR inhibitor and decreased by knockout of the autophagy gene Atg7. The autophagic regulation of STAT3 activation is likely mediated by induction of KAP1 degradation, because we showed that KAP1 directly interacted with STAT3 in the cytoplasm and knockdown of KAP1 increased the phosphorylation and nuclear translocation of STAT3. Subsequently, activated STAT3 transcriptionally upregulated the expression of BRCA1, which increased the ability of BM-MNCs to repair radiation-induced DNA damage. This novel finding that activation of autophagy can promote DNA damage repair in BM-MNCs via the ATG-KAP1-STAT3-BRCA1 pathway suggests that autophagy plays an important role in maintaining genomic integrity of BM-MNCs and its activation may confer protection of BM-MNCs against radiation-induced genotoxic stress. © 2017 by Radiation Research Society

©2017 by Radiation Research Society
Fei Xu, Xin Li, Lili Yan, Na Yuan, Yixuan Fang, Yan Cao, Li Xu, Xiaoying Zhang, Lan Xu, Chaorong Ge, Ni An, Gaoyue Jiang, Jialing Xie, Han Zhang, Jiayi Jiang, Xiaotian Li, Lei Yao, Suping Zhang, Daohong Zhou, and Jianrong Wang "Autophagy Promotes the Repair of Radiation-Induced DNA Damage in Bone Marrow Hematopoietic Cells via Enhanced STAT3 Signaling," Radiation Research 187(3), 382-396, (3 March 2017). https://doi.org/10.1667/RR14640.1
Received: 27 September 2016; Accepted: 19 December 2016; Published: 3 March 2017
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