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RAP80 is critical in maintaining genomic stability and suppressing tumor development.

The ubiquitin interaction motif-containing protein RAP80 was recently found to play a key role in DNA damage response (DDR) signaling by facilitating the translocation of several DDR mediators, including BRCA1, to ionizing irradiation (IR)-induced foci. In this study, we examine the effect of the loss of RAP80 on genomic stability and the susceptibility to cancer development in RAP80 null (RAP80(-/-)) mice. RAP80(-/-) mice are viable and did not exhibit any apparent developmental defects. Mouse embryonic fibroblasts (MEF) derived from RAP80(-/-) mice underwent premature senescence compared with wild-type (WT) MEFs, were more sensitive to IR, and exhibited a higher level of spontaneous and IR-induced genomic instability. RAP80(-/-) thymocytes were more sensitive to IR-induced cell death than WT thymocytes. RAP80(-/-) mice were more susceptible to spontaneous lymphoma development and the development of 7,12-dimethylbenz(a)anthracene-induced mammary gland tumors. Moreover, the loss of RAP80 accelerated tumor formation in both p53(-/-) and p53(+/-) mice. Our data indicate that RAP80-deficiency promotes genomic instability and causes an increase in cancer risk consistent with the concept that RAP80 exhibits a tumor suppressor function.

Pubmed ID: 22896338


  • Yin Z
  • Menendez D
  • Resnick MA
  • French JE
  • Janardhan KS
  • Jetten AM


Cancer research

Publication Data

October 1, 2012

Associated Grants

  • Agency: Intramural NIH HHS, Id: Z01 ES101586-06
  • Agency: NIEHS NIH HHS, Id: Z01-ES-101586
  • Agency: NIEHS NIH HHS, Id: Z01-ES065079

Mesh Terms

  • Animals
  • Benz(a)Anthracenes
  • Cell Aging
  • Cell Cycle Proteins
  • Cells, Cultured
  • Embryo, Mammalian
  • Female
  • Fibroblasts
  • Gene Expression Regulation, Neoplastic
  • Genomic Instability
  • Kaplan-Meier Estimate
  • Lymphoma
  • Male
  • Mammary Neoplasms, Experimental
  • Mice
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Reverse Transcriptase Polymerase Chain Reaction
  • Thymocytes
  • Transcription Factors
  • Tumor Suppressor Protein p53
  • Tumor Suppressor Proteins