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Measuring DNA Damage and Repair in Mouse Splenocytes After Chronic In Vivo Exposure to Very Low Doses of Beta- and Gamma-Radiation
Published on: July 3, 2015
Keratin 17 Impacts Global Gene Expression and Controls G2/M Cell Cycle Transition in Ionizing Radiation-Induced Skin
ZhiCao Yue1, JianQiong Lin1, XiaoPeng Lu2
1Department of Cell Biology & Medical Genetics, Shenzhen University Medical School, Shenzhen, China; International Cancer Center, Shenzhen University Medical School, Shenzhen, China; Guangdong Key Laboratory of Genome Instability and Human Disease Prevention, Shenzhen University Medical School, Shenzhen, China.
Abstract:
Keratin 17 (K17) is a cytoskeletal protein that is part of the intermediate filaments in epidermal keratinocytes. In K17-/- mice, ionizing radiation induced more severe hair follicle damage, whereas the epidermal inflammatory response was attenuated compared with that in wild-type mice. Both p53 and K17 have a major impact on global gene expression because over 70% of the differentially expressed genes in the skin of wild-type mice showed no expression change in p53-/- or K17-/- skin after ionizing radiation. K17 does not interfere with the dynamics of p53 activation; rather, global p53 binding in the genome is altered in K17-/- mice. The absence of K17 leads to aberrant cell cycle progression and mitotic catastrophe in epidermal keratinocytes, which is due to nuclear retention, thus reducing the degradation of B-Myb, a key regulator of the G2/M cell cycle transition. These results expand our understanding of the role of K17 in regulating global gene expression and ionizing radiation-induced skin damage.
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