scholarly journals ATR Regulates a G2-Phase Cell-Cycle Checkpoint in Arabidopsis thaliana

2004 ◽  
Vol 16 (5) ◽  
pp. 1091-1104 ◽  
Author(s):  
Kevin Culligan ◽  
Alain Tissier ◽  
Anne Britt
Oncogene ◽  
1997 ◽  
Vol 15 (7) ◽  
pp. 749-758 ◽  
Author(s):  
B G Gabrielli ◽  
J M Clark ◽  
A K McCormack ◽  
K A O Ellem

Oncogenesis ◽  
2021 ◽  
Vol 10 (5) ◽  
Author(s):  
Madushan Fernando ◽  
Pascal H. G. Duijf ◽  
Martina Proctor ◽  
Alexander J. Stevenson ◽  
Anna Ehmann ◽  
...  

AbstractDefective DNA repair is being demonstrated to be a useful target in cancer treatment. Currently, defective repair is identified by specific gene mutations, however defective repair is a common feature of cancers without these mutations. DNA damage triggers cell cycle checkpoints that are responsible for co-ordinating cell cycle arrest and DNA repair. Defects in checkpoint signalling components such as ataxia telangiectasia mutated (ATM) occur in a low proportion of cancers and are responsible for reduced DNA repair and increased genomic instability. Here we have investigated the AURKA-PLK1 cell cycle checkpoint recovery pathway that is responsible for exit from the G2 phase cell cycle checkpoint arrest. We demonstrate that dysregulation of PP6 and AURKA maintained elevated PLK1 activation to promote premature exit from only ATM, and not ATR-dependent checkpoint arrest. Surprisingly, depletion of the B55α subunit of PP2A that negatively regulates PLK1 was capable of overcoming ATM and ATR checkpoint arrests. Dysregulation of the checkpoint recovery pathway reduced S/G2 phase DNA repair efficiency and increased genomic instability. We found a strong correlation between dysregulation of the PP6-AURKA-PLK1-B55α checkpoint recovery pathway with signatures of defective homologous recombination and increased chromosomal instability in several cancer types. This work has identified an unrealised source of G2 phase DNA repair defects and chromosomal instability that are likely to be sensitive to treatments targeting defective repair.


Genetics ◽  
2003 ◽  
Vol 164 (1) ◽  
pp. 323-334
Author(s):  
S B Preuss ◽  
A B Britt

Abstract Although it is well established that plant seeds treated with high doses of gamma radiation arrest development as seedlings, the cause of this arrest is unknown. The uvh1 mutant of Arabidopsis is defective in a homolog of the human repair endonuclease XPF, and uvh1 mutants are sensitive to both the toxic effects of UV and the cytostatic effects of gamma radiation. Here we find that gamma irradiation of uvh1 plants specifically triggers a G2-phase cell cycle arrest. Mutants, termed suppressor of gamma (sog), that suppress this radiation-induced arrest and proceed through the cell cycle unimpeded were recovered in the uvh1 background; the resulting irradiated plants are genetically unstable. The sog mutations fall into two complementation groups. They are second-site suppressors of the uvh1 mutant's sensitivity to gamma radiation but do not affect the susceptibility of the plant to UV radiation. In addition to rendering the plants resistant to the growth inhibitory effects of gamma radiation, the sog1 mutation affects the proper development of the pollen tetrad, suggesting that SOG1 might also play a role in the regulation of cell cycle progression during meiosis.


EMBO Reports ◽  
2009 ◽  
Vol 10 (9) ◽  
pp. 1029-1035 ◽  
Author(s):  
Nianxiang Zhang ◽  
Ramandeep Kaur ◽  
Shamima Akhter ◽  
Randy J Legerski

Oncogene ◽  
2005 ◽  
Vol 24 (6) ◽  
pp. 1128-1128
Author(s):  
Christoph Joerges ◽  
Inge Kuntze ◽  
Thomas Herzinge

2010 ◽  
Vol 55 (2) ◽  
pp. 745-755 ◽  
Author(s):  
Mark D. Lavine ◽  
Gustavo Arrizabalaga

ABSTRACTMonensin is a polyether ionophore antibiotic that is widely used in the control of coccidia in animals. Despite its significance in veterinary medicine, little is known about its mode of action and potential mechanisms of resistance in coccidian parasites. Here we show that monensin causes accumulation of the coccidianToxoplasma gondiiat an apparent late-S-phase cell cycle checkpoint. In addition, experiments utilizing a monensin-resistantT. gondiimutant show that this effect of monensin is dependent on the function of a mitochondrial homologue of the MutS DNA damage repair enzyme (TgMSH-1). Furthermore, the same TgMSH-1-dependent cell cycle disruption is observed with the antiparasitic ionophore salinomycin and the DNA alkylating agent methyl nitrosourea. Our results suggest a novel mechanism for the mode of action of monensin and salinomycin on coccidial parasites, in which the drug activates an MSH-1-dependent cell cycle checkpoint by an unknown mechanism, ultimately leading to the death of the parasite. This model would indicate that cell cycle disruption is an important mediator of drug susceptibility and resistance to ionophoric antibiotics in coccidian parasites.


2004 ◽  
Vol 13 (2) ◽  
pp. 81-91 ◽  
Author(s):  
Jos?? Antonio L??pez-Guerrero ◽  
Concha L??pez-Gin??s ◽  
Antonio Pell??n ◽  
Carmen Carda ◽  
Antonio Llombart-Bosch

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