Bacteria Prefer Larger DNA

DNA polymerase I from Escherichia coli works best with DNA bases that are larger than those found in natural DNA, a new study finds. Eric T. Kool of Stanford University, John M. Essigmann of MIT, and coworkers used analogs of the base thymine to probe how small size differences affect the efficiency and fidelity of the polymerase, which is one of the enzymes that synthesize the bacterium’s DNA (Proc. Natl. Acad. Sci. USA 2005, 102, 15803). The researchers incrementally changed the size of the base over a 1-Å range by replacing the oxygen atoms in different analogs with hydrogen and the halogens through iodine. Kinetic studies revealed that the replication efficiency and fidelity increase with increasing base size, peaking at the chlorinated analog, which is larger than the natural base. The authors achieved similar results in vitro and in live E. coli. They suggest that the extra room in the enzyme may be an evolutionary tool to allow mutations or mismatches to sneak through occasionally.