Activation and Regulation of Polymerase V During DNA Synthesis
Myron F Goodman, Ph.D.
University of Southern California
NIEHS Grant R01ES012259
When a cell’s DNA replication machinery reaches damaged DNA, it must either repair or bypass the damage to copy its genome. In E. coli, the enzyme polymerase V can copy past damaged DNA, but it often introduces new mistakes when copying undamaged DNA. NIEHS grantees have discovered new details about the molecular basis for polymerase V activation, and a unique regulatory mechanism that limits polymerase V synthesis to the short DNA segments where it is needed. Understanding the role of DNA polymerases, in either inducing or preventing mutations, will have wide-ranging implications for understanding disease initiation or progression, and individual susceptibility, as well as determining treatment and prevention strategies.
The investigators used biochemical techniques to better understand how binding to the RecA protein and adenosine triphosphate (ATP) activates polymerase V. They found thatthe enzyme must bind to an ATP molecule before attaching to the DNA, and it must remain bound to ATP during DNA synthesis. The enzyme then breaks down the molecule of ATP to free itself from the DNA. Although the RecA protein can also break down the ATP, the researchers found that mutant RecA lacking this ability can still trigger DNA polymerase V to break down ATP itself.
No DNA polymerase has been observed to be regulated by ATP in this way. According to the researchers, this extra control would limit DNA polymerase V to copying damaged DNA and keep it from copying neighbouring stretches of undamaged DNA where it would likely introduce new errors.
Citation: Erdem AL, Jaszczur M, Bertram JG, Woodgate R, Cox MM, Goodman MF. 2014. DNA polymerase V activity is autoregulated by a novel intrinsic DNA-dependent ATPase. eLife 3:e02384.
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