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A potential role for LIM protein Ajuba in repression of DNA damage response in human cells
Author(s) -
Kalan Sampada,
Matveyenko Anastasiya,
Loayza Diego
Publication year - 2013
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.27.1_supplement.546.2
Subject(s) - shelterin , dna damage , microbiology and biotechnology , telomere , biology , immunoprecipitation , psychological repression , chromatin , dna , gene , genetics , dna binding protein , transcription factor , gene expression
Mammalian telomeres are specialized DNA‐protein structures located at each end of chromosomes. Telomeric DNA is bound by a six‐protein complex called shelterin, which prevents DNA damage response activation at the ends. In addition to shelterin, several accessory proteins associate with telomeres and assist in proper functioning of the complex. Our laboratory has discovered interaction between shelterin and LIM domain proteins. Of those, TRIP6 and LPP participate in the repression of the DNA damage response at telomeres. Here, using immunoprecipitation, we show that another LIM protein, Ajuba, associates with POT1 in tumor cells. Ajuba was detected at telomeres by chromatin immunoprecipitation. We also discovered that depletion of Ajuba by siRNA caused decrease in cell proliferation and increase in DNA damage response. An overall increase in p53‐BP1 damage foci was observed in nuclei of Ajuba‐depleted cells. By using FACS analysis, we observed an accumulation of cells in S phase. An activation of p53 with concomitant hyperphosphorylation of Rb was observed. Our results point to a vital role of Ajuba in the repression of endogenous DNA damage response in tumor cells, and could provide insights in understanding of senescence or immortalization of human cells. This research was funded by National Center for Research Resources (NCRR), a component of the National Institutes of Health (NIH).