p53 modulates BLM and WRN helicase activities 1 JBC Papers in Press. Published on June 21, 2002 as Manuscript M204111200 SUMMARY BLM, WRN and p53 are involved in the homologous DNA recombination pathway. The DNA structure-specific helicases, BLM and WRN, unwind Holliday junctions (HJ), an activity that could suppress inappropriate homologous recombination during DNA replication. Here, we show that purified, recombinant p53 binds to BLM and WRN helicases and attenuates their ability to unwind

more »

... thetic HJ in vitro. The p53 248W mutant reduces abilities both to bind HJ and to inhibit helicase activities, whereas the p53 273H mutant losses these abilities. Moreover, fulllength p53 and a C-terminal polypeptide (residues 373-383) inhibit the BLM and WRN helicase activities, but phosphorylation at Ser376 or Ser378 completely abolishes this inhibition. Following blockage of DNA replication, Ser15 phospho-p53, BLM and RAD51 colocalize in nuclear foci at sites likely to contain DNA replication intermediates in cells. Our results are consistent with a novel mechanism for p53-mediated regulation of DNA recombinational repair that involves p53 posttranslational modifications and functional protein-protein interactions with BLM and WRN DNA helicases.