Physical and functional interactions of the tumor suppressor protein p53 and DNA polymerase alpha-primase

Nucleic Acids Research
Christian Melle, Heinz-Peter Nasheuer

Abstract

The wild-type form of p53 contains an intrinsic 3'-5'-exonuclease activity. As p53 forms a complex with DNA polymerase alpha-primase (pol-prim) in vivo this finding suggests that p53 might cooperate with pol-prim to stabilize the genetic information of living cells. To test this hypothesis, exonuclease-free DNA pol-prim was expressed alone or together with p53 for purification. Pol-prim formed a complex with p53, which was purified by ion exchange and immunoaffinity chromatography from baculovirus-infected insect cells. The p53-containing pol-prim fractions removed a 3'-unpaired nucleotide with a 1.5-2-fold higher rate than a paired nucleotide, whereas the four subunit pol-prim did not have any exonuclase activity. Therefore, only p53/pol-prim was able to elongate a primer-template that contained a 3'-unpaired primer end in vitro. To achieve this, the 3'-5'-exonuclease activity of p53 excised the unpaired nucleotide at the 3'-end of the primer and created a paired 3'-end, which pol-prim was able to elongate. The exonuclease activity of p53 as well as the elongation of a primer with a mispaired 3'-end was inhibited specifically by the anti-p53 monoclonal antibodies PAb240 and PAb421.

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Aug 19, 2007·Journal of Molecular Medicine : Official Organ of the Gesellschaft Deutscher Naturforscher Und Ärzte·Mary BakhanashviliGalia Rahav
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