scholarly journals A role for the DNA-damage checkpoint kinase Chk1 in the virulence program of the fungus Ustilago maydis

2009 ◽  
Vol 122 (22) ◽  
pp. 4130-4140 ◽  
Author(s):  
N. Mielnichuk ◽  
C. Sgarlata ◽  
J. Perez-Martin
Keyword(s):  
Dna Damage ◽  
Ustilago Maydis ◽  
Dna Damage Checkpoint ◽  
Checkpoint Kinase

scholarly journals Ubiquitination of the DNA-damage checkpoint kinase CHK1 by TRAF4 is required for CHK1 activation

2020 ◽  
Vol 13 (1) ◽  
Author(s):  
Xinfang Yu ◽  
Wei Li ◽  
Haidan Liu ◽  
Qipan Deng ◽  
Xu Wang ◽  
...  
Keyword(s):  
Dna Damage ◽  
Dna Damage Checkpoint ◽  
Checkpoint Kinase

scholarly journals Distinct Phosphatases Mediate the Deactivation of the DNA Damage Checkpoint Kinase Rad53

2008 ◽  
Vol 283 (25) ◽  
pp. 17123-17130 ◽  
Author(s):  
Anna Travesa ◽  
Alba Duch ◽  
David G. Quintana
Keyword(s):  
Dna Damage ◽  
Dna Damage Checkpoint ◽  
Checkpoint Kinase

scholarly journals Breaching the DNA damage checkpoint via PF-00477736, a novel small-molecule inhibitor of checkpoint kinase 1

2008 ◽  
Vol 7 (8) ◽  
pp. 2394-2404 ◽  
Author(s):  
Alessandra Blasina ◽  
Jill Hallin ◽  
Enhong Chen ◽  
Maria Elena Arango ◽  
Eugenia Kraynov ◽  
...  
Keyword(s):  
Dna Damage ◽  
Small Molecule ◽  
Small Molecule Inhibitor ◽  
Dna Damage Checkpoint ◽  
Checkpoint Kinase ◽  
Checkpoint Kinase 1 ◽  
Molecule Inhibitor

scholarly journals Pharmacological Inhibition of WEE1 Potentiates the Antitumoral Effect of the dl922-947 Oncolytic Virus in Malignant Mesothelioma Cell Lines

2020 ◽  
Vol 21 (19) ◽  
pp. 7333
Author(s):  
Carmelina Antonella Iannuzzi ◽  
Paola Indovina ◽  
Iris Maria Forte ◽  
Sarah Di Somma ◽  
Anna Maria Malfitano ◽  
...  
Keyword(s):  
Dna Damage ◽  
Cell Lines ◽  
Malignant Mesothelioma ◽  
Chromatin Condensation ◽  
Protein A ◽  
Dna Lesions ◽  
Cell Cycle Checkpoint ◽  
Dna Damage Checkpoint ◽  
Antitumor Effects ◽  
Checkpoint Kinase

Malignant mesothelioma (MM) is a very aggressive asbestos-related cancer, for which no therapy proves to be effective. We have recently shown that the oncolytic adenovirus dl922-947 had antitumor effects in MM cell lines and murine xenografts. Previous studies demonstrated that dl922-947-induced host cell cycle checkpoint deregulation and consequent DNA lesions associated with the virus efficacy. However, the cellular DNA damage response (DDR) can counteract this virus action. Therefore, we assessed whether AZD1775, an inhibitor of the G2/M DNA damage checkpoint kinase WEE1, could enhance MM cell sensitivity to dl922-947. Through cell viability assays, we found that AZD1775 synergized with dl922-947 selectively in MM cell lines and increased dl922-947-induced cell death, which showed hallmarks of apoptosis (annexinV-positivity, caspase-dependency, BCL-XL decrease, chromatin condensation). Predictably, dl922-947 and/or AZD1775 activated the DDR, as indicated by increased levels of three main DDR players: phosphorylated histone H2AX (γ-H2AX), phospho-replication protein A (RPA)32, phospho-checkpoint kinase 1 (CHK1). Dl922-947 also increased inactive Tyr-15-phosphorylated cyclin-dependent kinase 1 (CDK1), a key WEE1 substrate, which is indicative of G2/M checkpoint activation. This increase in phospho-CDK1 was effectively suppressed by AZD1775, thus suggesting that this compound could, indeed, abrogate the dl922-947-induced DNA damage checkpoint in MM cells. Overall, our data suggest that the dl922-947-AZD1775 combination could be a feasible strategy against MM.

scholarly journals DNA damage checkpoint kinase Chk2 triggers replicative senescence

2004 ◽  
Vol 23 (13) ◽  
pp. 2554-2563 ◽  
Author(s):  
Véronique Gire ◽  
Pierre Roux ◽  
David Wynford-Thomas ◽  
Jean-Marc Brondello ◽  
Vjekoslav Dulic
Keyword(s):  
Dna Damage ◽  
Replicative Senescence ◽  
Dna Damage Checkpoint ◽  
Checkpoint Kinase
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