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GENOME EDITING. "Phylogenetic analyses as well as GenBank database comparisons show that most natural genome-editing competences are not of cellular origin but represent original skills of viruses." https://lnkd.in/e-pJFM6 View in LinkedIn

RX TARGETS. "Because DNA polymerases can help cancer cells tolerate DNA damage, some of these enzymes may be viable targets for therapeutic strategies." https://lnkd.in/e_FVkkp View in LinkedIn

MUTATIONS AND CANCER. "Many point mutations that occur in cancer cells arise from the error-generating activities of DNA polymerases. However, the ability of some of these enzymes to bypass DNA damage may actually defend against chromosome instability in cells and at least one DNA polymerase, POLζ, is a suppressor of spontaneous tumorigenesis." https://lnkd.in/e_FVkkp View in LinkedIn

MANY AVENUES. "Given the existence of many DNA polymerases whose fidelity can vary over a 10,000-fold range, and given the multiple and complex transactions that all require DNA synthesis to maintain genome stability, there are probably many more ways to generate mutant cells that thrive despite reduced DNA synthesis fidelity. Thus, the current list of associations between defective DNA synthesis fidelity and cancer is almost certainly incomplete." http://www.sciencedirect.com/science/article/pii/S1535610803000278 View in LinkedIn

TUMOR FORMATION. "Genomic instability refers to an increased tendency of alterations in the genome during the life cycle of cells. It is a major driving force for tumorigenesis." https://lnkd.in/bam9PGn View in LinkedIn

AMPLIFICATION EFFECT. "Here is a stunning example of the consequences of RNA polymerase error rates. Tens of millions of humans are infected with HIV-1, and every infected person produces billions of viral genomes per day, each with one mutation. Over 10(16) genomes are produced daily on the entire planet. As a consequence, thousands of mutants arise by chance every day that are resistant to every combination of antiviral compounds in use or in development." https://lnkd.in/e9SMJNz View in LinkedIn

RNA VIRUS MUTATION RATE. "Given a typical RNA viral genome of 10,000 bases, a mutation frequency of 1 in 10,000 corresponds to an average of 1 mutation in every replicated genome. If a single cell infected with poliovirus produces 10,000 new virus particles, this error rate means that in theory, about 10,000 new viral mutants have been produced. This enormous mutation rate explains why RNA viruses evolve so readily." https://lnkd.in/e9SMJNz View in LinkedIn

KINGS OF ERRORS. "Even though DNA polymerases have proofreading abilities, they still make mistakes – on the order of about one misincorporation per 10(7) to 10(9) nucleotides polymerized. But the RNA polymerases of RNA viruses are the kings of errors – these enzymes screw up as often as one time for every 1,000 – 100,000 nucleotides polymerized. This high rate of mutation comes from the lack of proofreading ability in RNA polymerases." https://lnkd.in/e9SMJNz View in LinkedIn

ERROR CONTROL. "Most polymerases lack intrinsic error-checking activity, relying on Watson–Crick base pairing for their fidelity. However, the proofreading (exonuclease) domains of Pol δ and Pol ɛ ensure that these polymerases have a particularly low error rate, of the order of 10(-7) substitution mutations per base. A variety of in vitro studies has shown that proofreading improves replication fidelity approximately 100-fold." https://lnkd.in/eXdfD76 View in LinkedIn

SO ENDS the contemplation of protein diversity on planet earth, the most common proteins, and the number of sequences experimented with by Evolution since life began. And how relatively few templates can give rise to startling diversity of protein structures, and how they in turn collaborate into yet more structures. This is surely a snapshot of an evolutionary machine of extraordinary wit and ingenuity. View in LinkedIn