Document Detail

Induction of a caffeine-sensitive S-phase cell cycle checkpoint by psoralen plus ultraviolet A radiation.
MedLine Citation:
PMID:  13679850     Owner:  NLM     Status:  MEDLINE    
Induction of interstrand crosslinks (ICLs) in chromosomal DNA is considered a major reason for the antiproliferative effect of psoralen plus ultraviolet A (PUVA). It is unclear as to whether PUVA-induced cell cycle arrest is caused by ICLs mechanically stalling replication forks or by triggering cell cycle checkpoints. Cell cycle checkpoints serve to maintain genomic stability by halting cell cycle progression to prevent replication of damaged DNA templates or segregation of broken chromosomes. Here, we show that HaCaT keratinocytes treated with PUVA arrest with S-phase DNA content. Cells that had completed DNA replication were not perturbed by PUVA and passed through mitosis. Cells treated with PUVA during G1-phase continued traversing G1 until arresting in early S-phase. PUVA induced rapid phosphorylation of the Chk1 checkpoint kinase at Ser345 and a concomitant decrease in Cdc25A levels. Chk1 phosphorylation, decrease of Cdc25 A levels and S-phase arrest were abolished by caffeine, demonstrating that active checkpoint signaling rather than passive mechanical blockage by ICLs causes the PUVA-induced replication arrest. Overexpression of Cdc25A only partially overrode the S-phase arrest, suggesting that additional signaling events implement PUVA-induced S-phase arrest.
Christoph Joerges; Inge Kuntze; Thomas Herzinger; Thomas Herzinge
Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Oncogene     Volume:  22     ISSN:  0950-9232     ISO Abbreviation:  Oncogene     Publication Date:  2003 Sep 
Date Detail:
Created Date:  2003-09-18     Completed Date:  2003-10-31     Revised Date:  2011-11-02    
Medline Journal Info:
Nlm Unique ID:  8711562     Medline TA:  Oncogene     Country:  England    
Other Details:
Languages:  eng     Pagination:  6119-28     Citation Subset:  IM    
Klinik und Poliklinik für Dermatologie und Allergologie, Ludwig-Maximilians-University, Frauenlobstr. 9-11, D-80337 Munich, Germany.
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MeSH Terms
Caffeine / metabolism*
Cell Cycle / physiology,  radiation effects*
Cell Line
Cross-Linking Reagents / pharmacology*
DNA Replication / radiation effects
Fibroblasts / radiation effects
Ficusin / pharmacology*
Keratinocytes / radiation effects
Mitosis / radiation effects
Protein Kinases / metabolism,  radiation effects
S Phase / radiation effects
Serine / metabolism,  radiation effects
Ultraviolet Rays*
cdc25 Phosphatases / metabolism,  radiation effects
Reg. No./Substance:
0/Cross-Linking Reagents; 56-45-1/Serine; 58-08-2/Caffeine; 66-97-7/Ficusin; EC 2.7.-/Protein Kinases; EC kinase 1; EC protein, human; EC protein, rat; EC Phosphatases
Erratum In:
Oncogene. 2005 Feb 3;24(6):1128
Note: Herzinge, Thomas [corrected to Herzinger, Thomas]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine

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