Linked Life Data

17687332

Source:http://linkedlifedata.com/resource/pubmed/id/17687332

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
7157
pubmed:dateCreated
2007-8-30
pubmed:abstractText
When telomeres are rendered dysfunctional through replicative attrition of the telomeric DNA or by inhibition of shelterin, cells show the hallmarks of ataxia telangiectasia mutated (ATM) kinase signalling. In addition, dysfunctional telomeres might induce an ATM-independent pathway, such as ataxia telangiectasia and Rad3-related (ATR) kinase signalling, as indicated by the phosphorylation of the ATR target CHK1 in senescent cells and the response of ATM-deficient cells to telomere dysfunction. However, because telomere attrition is accompanied by secondary DNA damage, it has remained unclear whether there is an ATM-independent pathway for the detection of damaged telomeres. Here we show that damaged mammalian telomeres can activate both ATM and ATR and address the mechanism by which the shelterin complex represses these two important DNA damage signalling pathways. We analysed the telomere damage response on depletion of either or both of the shelterin proteins telomeric repeat binding factor 2 (TRF2) and protection of telomeres 1 (POT1) from cells lacking ATM and/or ATR kinase signalling. The data indicate that TRF2 and POT1 act independently to repress these two DNA damage response pathways. TRF2 represses ATM, whereas POT1 prevents activation of ATR. Unexpectedly, we found that either ATM or ATR signalling is required for efficient non-homologous end-joining of dysfunctional telomeres. The results reveal how mammalian telomeres use multiple mechanisms to avoid DNA damage surveillance and provide an explanation for the induction of replicative senescence and genome instability by shortened telomeres.
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
30
pubmed:volume
448
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
1068-71
pubmed:dateRevised
2011-11-2
pubmed:meshHeading
pubmed:year
2007
pubmed:articleTitle
Protection of telomeres through independent control of ATM and ATR by TRF2 and POT1.
pubmed:affiliation
Laboratory for Cell Biology and Genetics, The Rockefeller University, 1230 York Avenue, New York, New York 10021, USA.
pubmed:publicationType
Journal Article, Research Support, N.I.H., Extramural