Journal article
Lung Basal Stem Cells Rapidly Repair DNA Damage Using the Error-Prone Nonhomologous End-Joining Pathway
CE Weeden, Y Chen, SB Ma, Y Hu, G Ramm, KD Sutherland, GK Smyth, ML Asselin-Labat
Plos Biology | PUBLIC LIBRARY SCIENCE | Published : 2017
Abstract
Lung squamous cell carcinoma (SqCC), the second most common subtype of lung cancer, is strongly associated with tobacco smoking and exhibits genomic instability. The cellular origins and molecular processes that contribute to SqCC formation are largely unexplored. Here we show that human basal stem cells (BSCs) isolated from heavy smokers proliferate extensively, whereas their alveolar progenitor cell counterparts have limited colony-forming capacity. We demonstrate that this difference arises in part because of the ability of BSCs to repair their DNA more efficiently than alveolar cells following ionizing radiation or chemical-induced DNA damage. Analysis of mice harbouring a mutation in th..
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Awarded by UK Research and Innovation
Funding Acknowledgements
Australian Post-graduate Award. Received by CEW. The funder had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. Victorian State Government Operational Infrastructure Support. The funder had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. National Health and Medical Research Council (grant number 1058892 and 1054618). Received by GKS. The funder had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. Victorian Cancer Agency (grant number TS10-18). Received by MLAL. The funder had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. The Viertel Charitable Foundation Senior Medical Research Fellowship. Recevied by MLAL. The funder had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. CRC Cancer Therapeutics PhD Top-up Scholarship. Received by CEW. The funder had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. Australian Government NHMRC IRIISS. The funder had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.