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Papers Of The Week for October 27, 2006 [281 (43)]

A New Role for DNA Polymerase{diamondsuit}

Epigenetic gene silencing can result from modifications in gene expression due to changes in DNA methylation or chromatin structure. In Saccharomyces cerevisiae, DNA polymerase {epsilon} (Pol {epsilon}) has been shown to bind to double-stranded DNA (dsDNA) and to participate in the stable inheritance of the silenced state of chromatin. Pol {epsilon} is a four-subunit complex that contains a catalytic subunit, Pol2p, and three auxiliary subunits, Dpb2p, Dpb3p, and Dpb4p. Dpb3p and Dpb4p contain a histone-fold motif, and cells lacking DPB3 and/or DPB4 are defective in silencing, suggesting the subunits' involvement in dsDNA binding.Go


Figure 1
DNA polymerase {epsilon} binds to double-stranded DNA.

In this Paper of the Week, Toshiaki Tsubota and colleagues show that neither Pol2p-Dpb2p nor Dpb3p-Dpb4p binds stably to dsDNA but that binding is efficiently reconstituted when the two subassemblies are combined, indicating that both complexes are required for stable association with dsDNA. Further characterization of mutant forms of Pol {epsilon}, having amino acid substitutions in Dpb3p, suggests that the Dpb3p-Dpb4p subassembly in Pol {epsilon} binds dsDNA around its dimeric histone-fold structure in a manner resembling the histone-DNA interaction. The Pol {epsilon} mutants also displayed reduced telomeric silencing, suggesting that the dsDNA binding property of Pol {epsilon} is required for epigenetic silencing at telomeres.

FOOTNOTES

{diamondsuit} See referenced article, J. Biol. Chem. 2006, 281, 32898-32908 Back


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