Year: 2022

READ-WRITE GENOME. "Discoveries in cytogenetics, molecular biology, and genomics have revealed that genome change is an active cell-mediated physiological process. This is distinctly at variance with the pre-DNA assumption that genetic changes arise accidentally and sporadically. The discovery that DNA changes arise as the result of regulated cell biochemistry means that the genome is best modelled as a read–write (RW) data storage system rather than a read-only memory (ROM)." http://onlinelibrary.wiley.com/doi/10.1113/jphysiol.2014.271130/full View in LinkedIn

AUTO-SCRIPTING CELLS. "Cells write their own genome modifications. Now that we know about the regulated molecular processes that proofread, repair and modify genomic DNA, we can discuss the physiology of how cells protect the genome and write new genomic structures when appropriately stimulated." http://onlinelibrary.wiley.com/doi/10.1113/jphysiol.2014.271130/full View in LinkedIn

ENDONUCLEASE PROOFREADING. "Cellular DNA replication complexes contain exonuclease activities that come into play when an incorrect base has been incorporated onto the nascent DNA strand. Studies with Escherichia coli indicate that exonuclease proofreading removes about 99.9% of the accidental misincorporations from the nascent strand." http://onlinelibrary.wiley.com/doi/10.1113/jphysiol.2014.271130/full View in LinkedIn

ERROR RATE. "Although the six billion base pairs in each diploid human nucleus need to be duplicated prior to each cell division, they are vulnerable to destabilizing errors during replication. However, they ultimately occur at such low rates that approximately only one spontaneous error occurs per cell division (between 1 x 10(-9) and 1 x 10(-10) errors per bp)." https://lnkd.in/e9xgjd4 View in LinkedIn

POST-REPLICATION REPAIR. "For those misincorporations that escape exonuclease proofreading, cells have a backup mismatch repair system. Mismatch repair in E. coli removes about 99% of the post-replication incorporation errors." http://onlinelibrary.wiley.com/doi/10.1113/jphysiol.2014.271130/full View in LinkedIn

DOUBLE BACKUP PROOFREADING. "In summary, exonuclease proofreading plus mismatch repair can reduce error-driven mutations by five orders of magnitude in E. coli (and presumably by a similar degree in other organisms). These two physiological processes are homeostatic and respond to molecular sensing of double helix distortions." http://onlinelibrary.wiley.com/doi/10.1113/jphysiol.2014.271130/full View in LinkedIn

SOPHISTICATED DNA REPAIR SYSTEMS. "Joining two duplexes with double-strand (DS) breaks at their ends is today called ‘non-homologous end joining’ (NHEJ), and cells have various biochemical systems for carrying it out. NHEJ is but one of a series of biochemical systems that have evolved to protect genomes from many kinds of physical and chemical damage. The partial list...gives an idea of how extensive and sophisticated the physiology of DNA damage repair has evolved to be." http://onlinelibrary.wiley.com/doi/10.1113/jphysiol.2014.271130/full View in LinkedIn

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DNA DAMAGE CHECKPOINTS. "Critical to the operation of DNA repair systems is the ability cells have to delay progress through the cell cycle until repair is complete. The physiological process of monitoring each task in the cell cycle and controlling the overall cycle so that it remains synchronized is called a ‘checkpoint’." http://onlinelibrary.wiley.com/doi/10.1113/jphysiol.2014.271130/full View in LinkedIn

SELF-EVALUATION. "The reason checkpoints are so important is that they exemplify at the molecular level the processes of self-evaluation and self-control." http://onlinelibrary.wiley.com/doi/10.1113/jphysiol.2014.271130/full View in LinkedIn