Lung Basal Stem Cells Rapidly Repair DNA Damage Using the Error-Prone Nonhomologous End-Joining Pathway
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{"title"=>"Lung Basal Stem Cells Rapidly Repair DNA Damage Using the Error-Prone Nonhomologous End-Joining Pathway", "type"=>"journal", "authors"=>[{"first_name"=>"Clare E.", "last_name"=>"Weeden", "scopus_author_id"=>"56495128900"}, {"first_name"=>"Yunshun", "last_name"=>"Chen", "scopus_author_id"=>"55233004900"}, {"first_name"=>"Stephen B.", "last_name"=>"Ma", "scopus_author_id"=>"57193223713"}, {"first_name"=>"Yifang", "last_name"=>"Hu", "scopus_author_id"=>"35215059500"}, {"first_name"=>"Georg", "last_name"=>"Ramm", "scopus_author_id"=>"7006307479"}, {"first_name"=>"Kate D.", "last_name"=>"Sutherland", "scopus_author_id"=>"7006886664"}, {"first_name"=>"Gordon K.", "last_name"=>"Smyth", "scopus_author_id"=>"7102522582"}, {"first_name"=>"Marie Liesse", "last_name"=>"Asselin-Labat", "scopus_author_id"=>"10939408800"}], "year"=>2017, "source"=>"PLoS Biology", "identifiers"=>{"issn"=>"15457885", "pui"=>"614347154", "doi"=>"10.1371/journal.pbio.2000731", "sgr"=>"85011884966", "isbn"=>"1111111111", "pmid"=>"28125611", "scopus"=>"2-s2.0-85011884966"}, "id"=>"0d2f494d-79a8-34b6-8994-eb8e8fda4745", "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.Wedemonstrate 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 the DNA-dependent pro- tein kinase catalytic subunit (DNA-PKcs), a key enzyme in DNA damage repair by nonho- mologous end joining (NHEJ), indicated that BSCs preferentially repair their DNA by this error-prone process. Interestingly, polyploidy, a phenomenon associated with genetically unstable cells, was only observed in the human BSC subset. Expression signature analysis indicated that BSCs are the likely cells of origin of human SqCC and that high levels of NHEJ genes in SqCC are correlated with increasing genomic instability. Hence, our results favour a model in which heavy smoking promotes proliferation of BSCs, and their predilec- tion for error-prone NHEJ could lead to the high mutagenic burden that culminates in SqCC. Targeting DNA repair processes may therefore have a role in the prevention and therapy of SqCC.", "link"=>"http://www.mendeley.com/research/lung-basal-stem-cells-rapidly-repair-dna-damage-using-errorprone-nonhomologous-endjoining-pathway", "reader_count"=>22, "reader_count_by_academic_status"=>{"Unspecified"=>1, "Professor > Associate Professor"=>1, "Researcher"=>7, "Student > Ph. D. Student"=>6, "Student > Master"=>1, "Other"=>1, "Student > Bachelor"=>4, "Professor"=>1}, "reader_count_by_user_role"=>{"Unspecified"=>1, "Professor > Associate Professor"=>1, "Researcher"=>7, "Student > Ph. D. Student"=>6, "Student > Master"=>1, "Other"=>1, "Student > Bachelor"=>4, "Professor"=>1}, "reader_count_by_subject_area"=>{"Unspecified"=>3, "Engineering"=>1, "Biochemistry, Genetics and Molecular Biology"=>5, "Agricultural and Biological Sciences"=>8, "Medicine and Dentistry"=>2, "Pharmacology, Toxicology and Pharmaceutical Science"=>1, "Computer Science"=>1, "Immunology and Microbiology"=>1}, "reader_count_by_subdiscipline"=>{"Engineering"=>{"Engineering"=>1}, "Medicine and Dentistry"=>{"Medicine and Dentistry"=>2}, "Immunology and Microbiology"=>{"Immunology and Microbiology"=>1}, "Agricultural and Biological Sciences"=>{"Agricultural and Biological Sciences"=>8}, "Computer Science"=>{"Computer Science"=>1}, "Biochemistry, Genetics and Molecular Biology"=>{"Biochemistry, Genetics and Molecular Biology"=>5}, "Unspecified"=>{"Unspecified"=>3}, "Pharmacology, Toxicology and Pharmaceutical Science"=>{"Pharmacology, Toxicology and Pharmaceutical Science"=>1}}, "reader_count_by_country"=>{"United States"=>1, "United Kingdom"=>1}, "group_count"=>1}

Scopus | Further Information

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