Etoposide Induces Nuclear Re-Localisation of AID
- Publication Date
- December 04, 2013
- Journal
- PLOS ONE
- Authors
- Laurens J. Lambert, Simon Walker, Jack Feltham, Heather J. Lee, et al
- Volume
- 8
- Issue
- 12
- Pages
- e82110
- DOI
- https://dx.plos.org/10.1371/journal.pone.0082110
- Publisher URL
- http://journals.plos.org/plosone/article?id=10.1371%2Fjournal.pone.0082110
- PubMed
- http://www.ncbi.nlm.nih.gov/pubmed/24324754
- PubMed Central
- http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3852760
- Europe PMC
- http://europepmc.org/abstract/MED/24324754
- Web of Science
- 000327949300131
- Scopus
- 84891757651
- Mendeley
- http://www.mendeley.com/research/etoposide-induces-nuclear-relocalisation-aid
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Mendeley | Further Information
{"title"=>"Etoposide induces nuclear re-localisation of AID", "type"=>"journal", "authors"=>[{"first_name"=>"Laurens J.", "last_name"=>"Lambert", "scopus_author_id"=>"55992016900"}, {"first_name"=>"Simon", "last_name"=>"Walker", "scopus_author_id"=>"57198868819"}, {"first_name"=>"Jack", "last_name"=>"Feltham", "scopus_author_id"=>"57200333785"}, {"first_name"=>"Heather J.", "last_name"=>"Lee", "scopus_author_id"=>"16316055200"}, {"first_name"=>"Wolf", "last_name"=>"Reik", "scopus_author_id"=>"7007161076"}, {"first_name"=>"Jonathan", "last_name"=>"Houseley", "scopus_author_id"=>"8632992500"}], "year"=>2013, "source"=>"PLoS ONE", "identifiers"=>{"scopus"=>"2-s2.0-84891757651", "pmid"=>"24324754", "sgr"=>"84891757651", "doi"=>"10.1371/journal.pone.0082110", "isbn"=>"1932-6203", "issn"=>"19326203", "pui"=>"372069597"}, "id"=>"9025a02e-2625-3733-94d1-d83282a676c9", "abstract"=>"During B cell activation, the DNA lesions that initiate somatic hypermutation and class switch recombination are introduced by activation-induced cytidine deaminase (AID). AID is a highly mutagenic protein that is maintained in the cytoplasm at steady state, however AID is shuttled across the nuclear membrane and the protein transiently present in the nucleus appears sufficient for targeted alteration of immunoglobulin loci. AID has been implicated in epigenetic reprogramming in primordial germ cells and cell fusions and in induced pluripotent stem cells (iPS cells), however AID expression in non-B cells is very low. We hypothesised that epigenetic reprogramming would require a pathway that instigates prolonged nuclear residence of AID. Here we show that AID is completely re-localised to the nucleus during drug withdrawal following etoposide treatment, in the period in which double strand breaks (DSBs) are repaired. Re-localisation occurs 2-6 hours after etoposide treatment, and AID remains in the nucleus for 10 or more hours, during which time cells remain live and motile. Re-localisation is cell-cycle dependent and is only observed in G2. Analysis of DSB dynamics shows that AID is re-localised in response to etoposide treatment, however re-localisation occurs substantially after DSB formation and the levels of re-localisation do not correlate with γH2AX levels. We conclude that DSB formation initiates a slow-acting pathway which allows stable long-term nuclear localisation of AID, and that such a pathway may enable AID-induced DNA demethylation during epigenetic reprogramming.", "link"=>"http://www.mendeley.com/research/etoposide-induces-nuclear-relocalisation-aid", "reader_count"=>20, "reader_count_by_academic_status"=>{"Professor > Associate Professor"=>1, "Researcher"=>6, "Student > Doctoral Student"=>1, "Student > Ph. D. Student"=>9, "Lecturer"=>1, "Professor"=>2}, "reader_count_by_user_role"=>{"Professor > Associate Professor"=>1, "Researcher"=>6, "Student > Doctoral Student"=>1, "Student > Ph. D. Student"=>9, "Lecturer"=>1, "Professor"=>2}, "reader_count_by_subject_area"=>{"Unspecified"=>2, "Biochemistry, Genetics and Molecular Biology"=>5, "Agricultural and Biological Sciences"=>12, "Medicine and Dentistry"=>1}, "reader_count_by_subdiscipline"=>{"Medicine and Dentistry"=>{"Medicine and Dentistry"=>1}, "Agricultural and Biological Sciences"=>{"Agricultural and Biological Sciences"=>12}, "Biochemistry, Genetics and Molecular Biology"=>{"Biochemistry, Genetics and Molecular Biology"=>5}, "Unspecified"=>{"Unspecified"=>2}}, "group_count"=>0}Scopus | Further Information
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Wikipedia | Further Information
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Relative Metric
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