“When the DNA double helix was first revealed by Watson and Crick in 1953, its structure seemed perfect and robust, well-designed to resist most of the disruptive influences that might be present inside living cells. For example, the bases in the double helix are turned inward and thus are not very susceptible to direct attack by chemical mutagens. Moreover, the linkages between adjacent bases were found to be resistant to cleavage by alkaline ions that arise continually in the cell.
“But while the double helix itself is relatively resistant to chemical attack, the process of maintaining a cell’s genetic integrity has a weak link. The vulnerability derives from the need to replicate the cell’s genome each time the cell goes through the process of growth and division. The resulting duplicate copies of the genome enable the mother cell to endow each of its daughters with a genome precisely equivalent to the one that it carries itself.
“This process of DNA replication has flaws. On occasion, a cell will miscopy a sequence of its DNA prior to cell division, and as a consequence, one of its daughters will receive a slightly miscopied genome, in effect a mutated one. Even the best-functioning cells will occasionally miscopy one in a million (or ten million) bases during each cycle of DNA replication. Hence, cell growth and division create vulnerability mutation.
“This imperfection suggested another way cancer formation might be accelerated. Agents that promote cell growth will indirectly create mutations simply because they force cells to replicate their DNA. More DNA copying means more inadvertent copying mistakes, hence more mistakes.”
Book Blurbs 