American Association for Cancer Research
00085472can121484-sup-f4_870k.pdf (870.73 kB)

Supplementary Figure 4 from RAP80 Is Critical in Maintaining Genomic Stability and Suppressing Tumor Development

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journal contribution
posted on 2023-03-30, 21:28 authored by Zhengyu Yin, Daniel Menendez, Michael A. Resnick, John E. French, Kyathanahalli S. Janardhan, Anton M. Jetten

PDF file - 870K, Increased chromosomal instability in RAP80-/- iMEFs after DNA damage



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. Cancer Res; 72(19); 5080–90. ©2012 AACR.