Abstract
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 Ser(376) or Ser(378) completely abolishes this inhibition. Following blockage of DNA replication, Ser(15) 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.
DOI
10.1074/jbc.m204111200
Publication Date
2002-08-01
Publication Title
Journal of Biological Chemistry
Volume
277
Issue
35
Publisher
Elsevier BV
ISSN
0021-9258
Embargo Period
2024-11-19
First Page
31980
Last Page
31987
Recommended Citation
Yang, Q., Zhang, R., Wang, X., Spillare, E., & et al. (2002) 'The Processing of Holliday Junctions by BLM and WRN Helicases Is Regulated by p53', Journal of Biological Chemistry, 277(35), pp. 31980-31987. Elsevier BV: Available at: https://doi.org/10.1074/jbc.m204111200
