caa a22 4500 463185552 CHVBK 20180406164851.0 cr unu---uuuuu 170326e20070401xx s 000 0 eng 10.1007/s00726-006-0473-0 doi (NATIONALLICENCE)springer-10.1007/s00726-006-0473-0 Golubnitschaja O. Department of Radiology, Friedrich-Wilhelms-University of Bonn, Bonn, Germany aut Cell cycle checkpoints: the role and evaluation for early diagnosis of senescence, cardiovascular, cancer, and neurodegenerative diseases [Elektronische Daten] [O. Golubnitschaja] Summary.: Maintenance of genomic integrity is critical for prevention of a wide variety of adverse cellular effects including apoptosis, cellular senescence, and malignant cell transformation. Under stress conditions and even during an unperturbed cell cycle, checkpoint proteins play the key role in genome maintenance by and mediating cellular response to DNA damage, and represent an essential part of the "cellular stress response proteome”. Intact checkpoint signal transduction cascades check the presence of genome damage, trigger cell cycle arrest, and forward the information to the protein core of cell cycle machinery, replication apparatus, repair, and/or apoptotic protein cores. Genetic checkpoint defects lead to syndromes that demonstrate chromosomal instability, increased sensitivity to genotoxic stress, tissue degeneration, developmental retardation, premature aging, and cancer predisposition that is most extensively studied for the ATM-checkpoint mutated in Ataxia telangiectasia. Tissue specific epigenetic control over the function of cell cycle checkpoints can be, further, misregulated by aberrant DNA methylation status. The consequent checkpoint dysregulation may result in tissue specific degenerative processes such as degeneration and calcification of heart aortic valves, diabetic cardiomyopathy, hyperhomocysteinemic cerebrovascular, peripheral vascular and coronary heart diseases, neurodegenerative disorders (Alzheimer and Parkinson diseases, amyotrophic lateral sclerosis, glaucoma), and accelerated aging frequently accompanied with cancer. This review focuses on the checkpoints shown to be crucial for unperturbed cell cycle regulation, dysregulation of which might be considered as a potential molecular marker for early diagnosis of and therapy efficiency in neurodegenerative, cardiovascular and cancer diseases. An application of the most potent detection technologies such as "Disease Proteomics and Transcriptomics” also considered here, allows a most specific selection of diagnostic markers. Springer-Verlag, 2006 Keywords: Stress response proteome - Cell cycle checkpoints - Epigenetic control - Cardiovascular and cancer diseases - Senescence and neurodegeneration - Early diagnosis and follow-up - Disease proteomics and transcriptomics nationallicence Amino Acids Springer-Verlag 32/3(2007-04-01), 359-371 0939-4451 32:3<359 2007 32 726 https://doi.org/10.1007/s00726-006-0473-0 text/html Onlinezugriff via DOI 1 review-article jats NATIONALLICENCE 856 40 https://doi.org/10.1007/s00726-006-0473-0 text/html Onlinezugriff via DOI NATIONALLICENCE 100 1- Golubnitschaja O. Department of Radiology, Friedrich-Wilhelms-University of Bonn, Bonn, Germany aut NATIONALLICENCE 773 0- Amino Acids Springer-Verlag 32/3(2007-04-01), 359-371 0939-4451 32:3<359 2007 32 726 Metadata rights reserved Springer special CC-BY-NC licence nationallicence BK010053 XK010053 XK010000 NATIONALLICENCE NATIONALLICENCE NL-springer