Linked Life Data

19668189

Source:http://linkedlifedata.com/resource/pubmed/id/19668189

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
7259
pubmed:dateCreated
2009-8-28
pubmed:abstractText
The reprogramming of differentiated cells to pluripotent cells (induced pluripotent stem (iPS) cells) is known to be an inefficient process. We recently reported that cells with short telomeres cannot be reprogrammed to iPS cells despite their normal proliferation rates, probably reflecting the existence of 'reprogramming barriers' that abort the reprogramming of cells with uncapped telomeres. Here we show that p53 (also known as Trp53 in mice and TP53 in humans) is critically involved in preventing the reprogramming of cells carrying various types of DNA damage, including short telomeres, DNA repair deficiencies, or exogenously inflicted DNA damage. Reprogramming in the presence of pre-existing, but tolerated, DNA damage is aborted by the activation of a DNA damage response and p53-dependent apoptosis. Abrogation of p53 allows efficient reprogramming in the face of DNA damage and the generation of iPS cells carrying persistent DNA damage and chromosomal aberrations. These observations indicate that during reprogramming cells increase their intolerance to different types of DNA damage and that p53 is critical in preventing the generation of human and mouse pluripotent cells from suboptimal parental cells.
pubmed:commentsCorrections
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Aug
pubmed:issn
1476-4687
pubmed:author
pubmed:issnType
Electronic
pubmed:day
27
pubmed:volume
460
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
1149-53
pubmed:meshHeading
pubmed:year
2009
pubmed:articleTitle
A p53-mediated DNA damage response limits reprogramming to ensure iPS cell genomic integrity.
pubmed:affiliation
Telomeres and Telomerase Group, Molecular Oncology Program, Spanish National Cancer Research Centre (CNIO), Melchor Fernández Almagro 3, Madrid E-28029, Spain.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't