Replication protein A, the laxative that keeps DNA regular: The importance of RPA phosphorylation in maintaining genome stability
| Autor: | Gregory G. Oakley, Brendan M. Byrne |
|---|---|
| Rok vydání: | 2019 |
| Předmět: |
DNA Replication
0301 basic medicine DNA damage Biology complex mixtures DNA-binding protein Genomic Instability Protein–protein interaction 03 medical and health sciences chemistry.chemical_compound 0302 clinical medicine Neoplasms Replication Protein A Humans Phosphorylation Replication protein A Genome DNA replication DNA Cell Biology Telomere Cell biology enzymes and coenzymes (carbohydrates) 030104 developmental biology chemistry 030217 neurology & neurosurgery Developmental Biology Nucleotide excision repair |
| Zdroj: | Seminars in Cell & Developmental Biology. 86:112-120 |
| ISSN: | 1084-9521 |
| Popis: | The eukaryotic ssDNA-binding protein, Replication protein A (RPA), was first discovered almost three decades ago. Since then, much progress has been made to elucidate the critical roles for RPA in DNA metabolic pathways that help promote genomic stability. The canonical RPA heterotrimer (RPA1-3) is an essential coordinator of DNA metabolism that interacts with ssDNA and numerous protein partners to coordinate its roles in DNA replication, repair, recombination and telomere maintenance. An alternative form of RPA, termed aRPA, is formed by a complex of RPA4 with RPA1 and RPA3. aRPA is expressed differentially in cells compared to canonical RPA and has been shown to inhibit canonical RPA function while allowing for regular maintenance of cell viability. Interestingly, while aRPA is defective in DNA replication and cell cycle progression, it was shown to play a supporting role in nucleotide excision repair and recombination. The binding domains of canonical RPA interact with a growing number of partners involved in numerous genome maintenance processes. The protein interactions of the RPA-ssDNA complex are not only governed by competition between the binding proteins but also by post-translation modifications such as phosphorylation. Phosphorylation of RPA2 is an important post-translational modification of the RPA complex, and is essential for directing context-specific functions of the RPA complex in the DNA damage response. Due to the importance of RPA in cellular metabolism, it was identified as an appealing target for chemotherapeutic drug development that could be used in future cancer treatment regimens. |
| Databáze: | OpenAIRE |
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