scholarly journals Protein kinase mutants of human ATR increase sensitivity to UV and ionizing radiation and abrogate cell cycle checkpoint control

1998 ◽  
Vol 95 (13) ◽  
pp. 7445-7450 ◽  
Author(s):  
J. A. Wright ◽  
K. S. Keegan ◽  
D. R. Herendeen ◽  
N. J. Bentley ◽  
A. M. Carr ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Protein Kinase ◽  
Ionizing Radiation ◽  
Cell Cycle Checkpoint ◽  
Checkpoint Control ◽  
Cycle Checkpoint

DNA damage checkpoint kinases in cancer

2020 ◽  
Vol 22 ◽  
Author(s):  
Hannah L. Smith ◽  
Harriet Southgate ◽  
Deborah A. Tweddle ◽  
Nicola J. Curtin
Keyword(s):  
Cell Cycle ◽  
Dna Damage ◽  
Environmental Dna ◽  
Cell Cycle Checkpoint ◽  
Checkpoint Control ◽  
Integrated Network ◽  
Checkpoint Kinases ◽  
G1 Checkpoint ◽  
Cycle Checkpoint ◽  
High Level

Abstract DNA damage response (DDR) pathway prevents high level endogenous and environmental DNA damage being replicated and passed on to the next generation of cells via an orchestrated and integrated network of cell cycle checkpoint signalling and DNA repair pathways. Depending on the type of damage, and where in the cell cycle it occurs different pathways are involved, with the ATM-CHK2-p53 pathway controlling the G1 checkpoint or ATR-CHK1-Wee1 pathway controlling the S and G2/M checkpoints. Loss of G1 checkpoint control is common in cancer through TP53, ATM mutations, Rb loss or cyclin E overexpression, providing a stronger rationale for targeting the S/G2 checkpoints. This review will focus on the ATM-CHK2-p53-p21 pathway and the ATR-CHK1-WEE1 pathway and ongoing efforts to target these pathways for patient benefit.

scholarly journals Xenopus Cds1 Is Regulated by DNA-Dependent Protein Kinase and ATR during the Cell Cycle Checkpoint Response to Double-Stranded DNA Ends

2004 ◽  
Vol 24 (22) ◽  
pp. 9968-9985 ◽  
Author(s):  
Troy D. McSherry ◽  
Paul R. Mueller
Keyword(s):  
Cell Cycle ◽  
Protein Kinase ◽  
Cell Cycle Checkpoint ◽  
Dual Function ◽  
Dependent Protein Kinase ◽  
Double Stranded Dna ◽  
Cycle Checkpoint ◽  
Protein Dissociation ◽  
Dependent Protein ◽  
Dna Ends

ABSTRACT The checkpoint kinase Cds1 (Chk2) plays a key role in cell cycle checkpoint responses with functions in cell cycle arrest, DNA repair, and induction of apoptosis. Proper regulation of Cds1 is essential for appropriate cellular responses to checkpoint-inducing insults. While the kinase ATM has been shown to be important in the regulation of human Cds1 (hCds1), here we report that the kinases ATR and DNA-dependent protein kinase (DNA-PK) play more significant roles in the regulation of Xenopus Cds1 (XCds1). Under normal cell cycle conditions, nonactivated XCds1 constitutively associates with a Xenopus ATR complex. The association of XCds1 with this complex does not require a functional forkhead activation domain but does require a putative SH3 binding region that is found in XCds1. In response to double-stranded DNA ends, the amino terminus of XCds1 is rapidly phosphorylated in a sequential pattern. First DNA-PK phosphorylates serine 39, a site not previously recognized as important in Cds1 regulation. Xenopus ATM, ATR, and/or DNA-PK then phosphorylate three consensus serine/glutamine sites. Together, these phosphorylations have the dual function of inducing dissociation from the ATR complex and independently promoting the full activation of XCds1. Thus, the checkpoint-mediated activation of XCds1 requires phosphorylation by multiple phosphoinositide 3-kinase-related kinases, protein-protein dissociation, and autophosphorylation.

Convergence of DNA repair and cell-cycle checkpoint control

2000 ◽  
Vol 2 (6) ◽  
pp. E95-E95 ◽  
Author(s):  
Angela Eggleston
Keyword(s):  
Cell Cycle ◽  
Dna Repair ◽  
Cell Cycle Checkpoint ◽  
Checkpoint Control ◽  
Cycle Checkpoint
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