Linked Life Data

20716119

Source:http://linkedlifedata.com/resource/pubmed/id/20716119

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
7
pubmed:dateCreated
2011-6-23
pubmed:abstractText
Besides the well-understood DNA damage response via establishment of G(2) checkpoint arrest, novel studies focus on the recovery from arrest by checkpoint override to monitor cell cycle re-entry. The aim of this study was to investigate the role of Chk1 in the recovery from G(2) checkpoint arrest in HCT116 (human colorectal cancer) wt, p53(-/-) and p21(-/-) cell lines following H(2) O(2) treatment. Firstly, DNA damage caused G(2) checkpoint activation via Chk1. Secondly, overriding G(2) checkpoint led to (i) mitotic slippage, cell cycle re-entry in G(1) and subsequent G(1) arrest associated with senescence or (ii) premature mitotic entry in the absence of p53/p21(WAF1) causing mitotic catastrophe. We revealed subtle differences in the initial Chk1-involved G(2) arrest with respect to p53/p21(WAF1) : absence of either protein led to late G(2) arrest instead of the classic G(2) arrest during checkpoint initiation, and this impacted the release back into the cell cycle. Thus, G(2) arrest correlated with downstream senescence, but late G(2) arrest led to mitotic catastrophe, although both cell cycle re-entries were linked to upstream Chk1 signalling. Chk1 knockdown deciphered that Chk1 defines long-term DNA damage responses causing cell cycle re-entry. We propose that recovery from oxidative DNA damage-induced G(2) arrest requires Chk1. It works as cutting edge and navigates cells to senescence or mitotic catastrophe. The decision, however, seems to depend on p53/p21(WAF1) . The general relevance of Chk1 as an important determinant of recovery from G(2) checkpoint arrest was verified in HT29 colorectal cancer cells.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Jul
pubmed:issn
1582-4934
pubmed:author
pubmed:copyrightInfo
© 2011 The Authors Journal of Cellular and Molecular Medicine © 2011 Foundation for Cellular and Molecular Medicine/Blackwell Publishing Ltd.
pubmed:issnType
Electronic
pubmed:volume
15
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
1528-41
pubmed:meshHeading
pubmed:year
2011
pubmed:articleTitle
Cutting edge: Chk1 directs senescence and mitotic catastrophe in recovery from G? checkpoint arrest.
pubmed:affiliation
Department of Pathology, Otto-von-Guericke University Magdeburg, Leipziger Strasse 44, Magdeburg, Germany. Angela.Poehlmann@med.ovgu.de
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't