LIM Protein Ajuba Participates in the Repression of ATR-Mediated DNA Damage Response in Human Cells
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چکیده
............................................................................................................................................... IV ACKNOWLEDGEMENTS ........................................................................................................................ V TABLE OF CONTENTS ........................................................................................................................ VII LIST OF ILLUSTRATIONS, CHARTS AND DIAGRAMS .................................................................. X CHAPTER 1: INTRODUCTION ............................................................................................................. 1 GENOMIC INTEGRITY ........................................................................................................................................ 1 CELL CYCLE CONTROL AND CANCER .......................................................................................................... 1 DNA DAMAGE RESPONSE ................................................................................................................................. 2 PHOSPHATIDYLINOSITOL (PI) 3-‐KINASE RELATED KINASES ........................................................ 3 ATR mediated DNA damage response ......................................................................................................... 4 DDR DURING TELOMERE DE-‐PROTECTION ............................................................................................ 7 REPLICATION PROTEIN A (RPA) .................................................................................................................. 9 LIM DOMAIN PROTEINS .................................................................................................................................. 11 Zyxin family of LIM proteins .......................................................................................................................... 16 Role of Zyxin family in DDR ............................................................................................................................ 17 Ajuba LIM protein .............................................................................................................................................. 18 OBJECTIVE OF THE THESIS ........................................................................................................................... 20 CHAPTER 2: MATERIALS AND METHODS .................................................................................... 22 CELL LINES AND ANTIBODIES ..................................................................................................................... 22 RNA INTERFERENCE USING SIRNA ............................................................................................................ 22 IMMUNOPRECIPITATION .............................................................................................................................. 23 IMMUNOFLUORENCE ...................................................................................................................................... 23
منابع مشابه
LIM Protein Ajuba Participates in the Repression of the ATR-Mediated DNA Damage Response
LIM proteins constitute a superfamily characterized by the presence of a LIM domain, known to be involved in protein-protein interactions. Our previous work has implicated members of the Zyxin family of LIM proteins, namely TRIP6 and LPP, in the repression of the DNA damage response (DDR) at telomeres. Here, we describe a role for Ajuba, a closely related LIM molecule, in repressing the ATR-med...
متن کاملThe Ajuba LIM domain protein is a corepressor for SNAG domain mediated repression and participates in nucleocytoplasmic Shuttling.
The SNAG repression domain is comprised of a highly conserved 21-amino acid sequence, is named for its presence in the Snail/growth factor independence-1 class of zinc finger transcription factors, and is present in a variety of proto-oncogenic transcription factors and developmental regulators. The prototype SNAG domain containing oncogene, growth factor independence-1, is responsible for the ...
متن کاملLIM protein Ajuba functions as a nuclear receptor corepressor and negatively regulates retinoic acid signaling.
Corepressors play an essential role in nuclear receptor-mediated transcriptional repression. In general, corepressors directly bind to nuclear receptors via CoRNR boxes (L/I-X-X-I/V-I) in the absence of ligand and appear to act as scaffolds to further recruit chromatin remodeling complexes to specific target genes. Here, we describe the identification of the multiple LIM domain protein Ajuba as...
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Following DNA damage that results in stalled replication fork, activation of ATR-CHK1 signaling induces the DNA damage response (DDR) in transformed cells. In the present studies on human cervical and breast cancer cells, we determined the effects of hsp90 inhibition on the levels and accumulation of DNA damage/repair-associated proteins following exposure to γ-ionizing radiation (IR; 4 Gy). We...
متن کاملThe LIM protein AJUBA recruits protein arginine methyltransferase 5 to mediate SNAIL-dependent transcriptional repression.
The SNAIL transcription factor contains C-terminal tandem zinc finger motifs and an N-terminal SNAG repression domain. The members of the SNAIL family have recently emerged as major contributors to the processes of development and metastasis via the regulation of epithelial-mesenchymal transition events during embryonic development and tumor progression. However, the mechanisms by which SNAIL r...
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تاریخ انتشار 2016