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p53 genes function to restrain mobile elements.

Genes & development | 2016

Throughout the animal kingdom, p53 genes govern stress response networks by specifying adaptive transcriptional responses. The human member of this gene family is mutated in most cancers, but precisely how p53 functions to mediate tumor suppression is not well understood. Using Drosophila and zebrafish models, we show that p53 restricts retrotransposon activity and genetically interacts with components of the piRNA (piwi-interacting RNA) pathway. Furthermore, transposon eruptions occurring in the p53(-) germline were incited by meiotic recombination, and transcripts produced from these mobile elements accumulated in the germ plasm. In gene complementation studies, normal human p53 alleles suppressed transposons, but mutant p53 alleles from cancer patients could not. Consistent with these observations, we also found patterns of unrestrained retrotransposons in p53-driven mouse and human cancers. Furthermore, p53 status correlated with repressive chromatin marks in the 5' sequence of a synthetic LINE-1 element. Together, these observations indicate that ancestral functions of p53 operate through conserved mechanisms to contain retrotransposons. Since human p53 mutants are disabled for this activity, our findings raise the possibility that p53 mitigates oncogenic disease in part by restricting transposon mobility.

Pubmed ID: 26701264 RIS Download

Research resources used in this publication

None found

Antibodies used in this publication

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Associated grants

  • Agency: NCI NIH HHS, United States
    Id: R01 CA135731
  • Agency: NIDDK NIH HHS, United States
    Id: T32 DK007307
  • Agency: NIGMS NIH HHS, United States
    Id: R01GM072124
  • Agency: NIDDK NIH HHS, United States
    Id: T32 5T32DK007307
  • Agency: NIGMS NIH HHS, United States
    Id: R01 GM115682
  • Agency: NCI NIH HHS, United States
    Id: R01CA135731
  • Agency: NIGMS NIH HHS, United States
    Id: R01 GM060518
  • Agency: NIGMS NIH HHS, United States
    Id: R01GM115682
  • Agency: NIGMS NIH HHS, United States
    Id: F31 GM108472
  • Agency: NIGMS NIH HHS, United States
    Id: T32 GM083831
  • Agency: NCI NIH HHS, United States
    Id: P30 CA142543
  • Agency: NIGMS NIH HHS, United States
    Id: 1F31GM108472-01
  • Agency: Howard Hughes Medical Institute, United States
  • Agency: NCI NIH HHS, United States
    Id: F31 CA189691
  • Agency: NCI NIH HHS, United States
    Id: 1F31CA189691-01
  • Agency: NIGMS NIH HHS, United States
    Id: GM060518
  • Agency: NIGMS NIH HHS, United States
    Id: R01 GM072124

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