The processing of holliday junctions by BLM and WRN helicases is regulated by p53

Qin Yang, Ran Zhang, Xin Wei Wang, Elisa A. Spillare, Steven P. Linke, Deepa Subramanian, Jack D. Griffith, Ji Ang Li, Ian D. Hickson, Jiang Cheng Shen, Lawrence A. Loeb, Sharlyn J. Mazur, Ettore Appella, Robert M. Brosh, Parimal Karmakar, Vilhelm A. Bohr, Curtis C. Harris

Research output: Contribution to journalArticlepeer-review

104 Scopus citations


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 synthetic HJ in vitro. The p53 248W mutant reduces abilities of both to bind HJ and inhibit helicase activities, whereas the p53 273H mutant loses these abilities. Moreover, full-length 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 post-translational modifications and functional protein-protein interactions with BLM and WRN DNA helicases.

Original languageEnglish
Pages (from-to)31980-31987
Number of pages8
JournalJournal of Biological Chemistry
Issue number35
StatePublished - Aug 30 2002


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