scholarly journals DNA Damage-induced Expression of p53 Suppresses Mitotic Checkpoint Kinase hMps1

2006 ◽  
Vol 281 (13) ◽  
pp. 8675-8685 ◽  
Author(s):  
Mandar R. Bhonde ◽  
Marie-Luise Hanski ◽  
Jan Budczies ◽  
Minh Cao ◽  
Bernd Gillissen ◽  
...  
Keyword(s):  
Dna Damage ◽  
Mitotic Checkpoint ◽  
Induced Expression ◽  
Checkpoint Kinase

scholarly journals Tethering DNA Damage Checkpoint Mediator Proteins Topoisomerase IIβ-binding Protein 1 (TopBP1) and Claspin to DNA Activates Ataxia-Telangiectasia Mutated and RAD3-related (ATR) Phosphorylation of Checkpoint Kinase 1 (Chk1)

2011 ◽  
Vol 286 (22) ◽  
pp. 19229-19236 ◽  
Author(s):  
Laura A. Lindsey-Boltz ◽  
Aziz Sancar
Keyword(s):  
Dna Damage ◽  
Ataxia Telangiectasia ◽  
Mammalian Cells ◽  
Binding Protein ◽  
Effector Proteins ◽  
Ataxia Telangiectasia Mutated ◽  
Checkpoint Kinase ◽  
Atr Kinase

The ataxia-telangiectasia mutated and RAD3-related (ATR) kinase initiates DNA damage signaling pathways in human cells after DNA damage such as that induced upon exposure to ultraviolet light by phosphorylating many effector proteins including the checkpoint kinase Chk1. The conventional view of ATR activation involves a universal signal consisting of genomic regions of replication protein A-covered single-stranded DNA. However, there are some indications that the ATR-mediated checkpoint can be activated by other mechanisms. Here, using the well defined Escherichia coli lac repressor/operator system, we have found that directly tethering the ATR activator topoisomerase IIβ-binding protein 1 (TopBP1) to DNA is sufficient to induce ATR phosphorylation of Chk1 in an in vitro system as well as in vivo in mammalian cells. In addition, we find synergistic activation of ATR phosphorylation of Chk1 when the mediator protein Claspin is also tethered to the DNA with TopBP1. Together, these findings indicate that crowding of checkpoint mediator proteins on DNA is sufficient to activate the ATR kinase.

scholarly journals A small increase in CHEK1 activity leads to the arrest of the first zygotic division in human

2020 ◽  
Author(s):  
Beili Chen ◽  
Jianying Guo ◽  
Ting Wang ◽  
Qianhui Lee ◽  
Jia Ming ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Dna Damage ◽  
Mitotic Checkpoint ◽  
Mitotic Division ◽  
Fine Tuning ◽  
Human Reproduction ◽  
Cycle Arrest ◽  
Assisted Human Reproduction ◽  
C Terminus ◽  
Low Concentrations

ABSTRACTThe first mitotic division in mammalian zygotes is unique. The fertilized egg reactivates its cell cycle, and the maternal and paternal genomes start to reprogram to become totipotent. The first division is very sensitive to a range of perturbations, particularly the DNA damage, leading to the embryo’s failure to enter the first mitosis. We discovered that a point mutation in the human CHEK1 gene resulted in an Arginine 442 to Glutamine change at the C-terminus of the CHEK1 protein. CHEK1 R442Q mutation caused the zygote to arrest just before the first division. Heterozygote individuals appeared to be healthy except that the female carriers are infertile. Expressing the corresponding mouse mutant Chk1 protein in zygotes also caused arrest before the first mitosis. Treating Chk1 R442Q mouse zygotes with low concentrations of CHEK1 inhibitor enabled the embryos to overcome the cell cycle arrest and resume normal development. Our results revealed an unexpected zygote mitotic checkpoint, which is extremely sensitive to the CHEK1 kinase activity. The fine-tuning of the DNA damage checkpoint permits the arrested one-cell embryos to overcome the first mitotic block and develop into healthy animals. These findings have important implications in assisted human reproduction.

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 Conformational Change of Human Checkpoint Kinase 1 (Chk1) Induced by DNA Damage

2016 ◽  
Vol 291 (25) ◽  
pp. 12951-12959 ◽  
Author(s):  
Xiangzi Han ◽  
Jinshan Tang ◽  
Jingna Wang ◽  
Feng Ren ◽  
Jinhua Zheng ◽  
...  
Keyword(s):  
Dna Damage ◽  
Conformational Change ◽  
Checkpoint Kinase ◽  
Checkpoint Kinase 1

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 Threonine-11, Phosphorylated by Rad3 and ATM In Vitro, Is Required for Activation of Fission Yeast Checkpoint Kinase Cds1

2001 ◽  
Vol 21 (10) ◽  
pp. 3398-3404 ◽  
Author(s):  
Katsunori Tanaka ◽  
Michael N. Boddy ◽  
Xiao-Bo Chen ◽  
Clare H. McGowan ◽  
Paul Russell
Keyword(s):  
Dna Damage ◽  
Dna Replication ◽  
Fission Yeast ◽  
Ataxia Telangiectasia ◽  
Null Mutant ◽  
Ataxia Telangiectasia Mutated ◽  
Tolerance Mechanisms ◽  
Checkpoint Kinase ◽  
And Function

ABSTRACT Fission yeast Cds1 is phosphorylated and activated when DNA replication is interrupted by nucleotide starvation or DNA damage. Cds1 enforces the S-M checkpoint that couples mitosis (M) to the completion of DNA synthesis (S). Cds1 also controls replicational stress tolerance mechanisms. Cds1 is regulated by a group of proteins that includes Rad3, a kinase related to human checkpoint kinase ATM (ataxia telangiectasia mutated). ATM phosphorylates serine or threonine followed by glutamine (SQ or TQ). Here we show that in vitro, Rad3 and ATM phosphorylate the N-terminal domain of Cds1 at the motif T11Q12. Substitution of threonine-11 with alanine (T11A) abolished Cds1 activation that occurs when DNA replication is inhibited by hydroxyurea (HU) treatment. Thecds1-T11A mutant was profoundly sensitive to HU, although not quite as sensitive as a cds1− null mutant. Cds1T11A was unable to enforce the S-M checkpoint. These results strongly suggest that Rad3-dependent phosphorylation of Cds1 at threonine-11 is required for Cds1 activation and function.

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 Inhibition of the checkpoint kinase Chk1 induces DNA damage and cell death in human Leukemia and Lymphoma cells

2014 ◽  
Vol 13 (1) ◽  
pp. 147 ◽  
Author(s):  
Christopher Bryant ◽  
Kirsten Scriven ◽  
Andrew J Massey
Keyword(s):  
Dna Damage ◽  
Cell Death ◽  
Human Leukemia ◽  
Lymphoma Cells ◽  
Checkpoint Kinase
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