About DNA polymerase...
January 21, 2015 8:56 PM Subscribe
Tomasetti and Vogelstein recently published an analysis that suggests the variation in the number of stem cell divisions leads to cancer incidence rates that are higher for tissues with relatively greater numbers of divisions. They recently posted a follow-up which attempts to address some of the counterarguments to their results. Acting on the premise that their work is correct or at least "in the right direction", are there labs or drug companies working on gene therapies that attempt to improve DNA polymerase fidelity (even in model organisms), as a means to one day perhaps reduce cancer incidence in higher-risk tissues? While it is easy through mutagenesis to worsen fidelity rates and increase cancer rates (as has been demo'ed in mice, say) can this aspect be engineered to be improved — that is, what biochemical aspects of (human) DNA polymerase have evolved to control its fidelity rate such that it might be possible to improve upon it?
Improving DNA polymerase fidelity is going to cause an awful lot of cells that would otherwise divide and be healthy to instead die, potentially causing tissue damage and developmental defects, particularly in a young growing animal. Less perfect DNA replication is one of the main mechanisms for repairing DNA damage. This isn't my area of expertise but I work with enough DNA damage people to be wary of this idea.
posted by shelleycat at 10:51 PM on January 21, 2015
posted by shelleycat at 10:51 PM on January 21, 2015
Though this doesn't directly answer your question about cancer models, it is worth noting that massive amounts of effort have been devoted to improving the fidelity (and other characteristics) of bacterial DNA polymerases for biotechnology purposes. Exploring that literature might help you understand what kinds of alterations to human DNA polymerase would improve fidelity.
posted by juliapangolin at 4:22 AM on January 22, 2015
posted by juliapangolin at 4:22 AM on January 22, 2015
This thread is closed to new comments.
posted by en forme de poire at 9:21 PM on January 21, 2015