Replication protein A (RPA): the eukaryotic SSB
- PMID: 10473346
- DOI: 10.1080/10409239991209255
Replication protein A (RPA): the eukaryotic SSB
Abstract
Replication protein A (RPA) is a heterotrimeric single-stranded DNA-binding protein that is highly conserved in eukaryotes. RPA plays essential roles in many aspects of nucleic acid metabolism, including DNA replication, nucleotide excision repair, and homologous recombination. In this review, we provide a comprehensive overview of RPA structure and function and highlight the more recent developments in these areas. The last few years have seen major advances in our understanding of the mechanism of RPA binding to DNA, including the structural characterization of the primary DNA-binding domains (DBD) and the identification of two secondary DBDs. Moreover, evidence indicates that RPA utilizes a multistep pathway to bind single-stranded DNA involving a particular molecular polarity of RPA, a mechanism that is apparently used to facilitate origin denaturation. In addition to its mechanistic roles, RPA interacts with many key factors in nucleic acid metabolism, and we discuss the critical nature of many of these interactions to DNA metabolism. RPA is a phosphorylation target for DNA-dependent protein kinase (DNA-PK) and likely the ataxia telangiectasia-mutated gene (ATM) protein kinase, and recent observations are described that suggest that RPA phosphorylation plays a significant modulatory role in the cellular response to DNA damage.
Similar articles
-
Functions of human replication protein A (RPA): from DNA replication to DNA damage and stress responses.J Cell Physiol. 2006 Aug;208(2):267-73. doi: 10.1002/jcp.20622. J Cell Physiol. 2006. PMID: 16523492 Free PMC article. Review.
-
Replication protein A interactions with DNA: differential binding of the core domains and analysis of the DNA interaction surface.Biochemistry. 2003 Nov 11;42(44):12909-18. doi: 10.1021/bi034930h. Biochemistry. 2003. PMID: 14596605
-
[Replication protein A as a major eukaryotic single-stranded DNA-binding protein and its role in DNA repair].Mol Biol (Mosk). 2016 Sep-Oct;50(5):735-750. doi: 10.7868/S0026898416030083. Mol Biol (Mosk). 2016. PMID: 27830676 Review. Russian.
-
Interactive Roles of DNA Helicases and Translocases with the Single-Stranded DNA Binding Protein RPA in Nucleic Acid Metabolism.Int J Mol Sci. 2017 Jun 8;18(6):1233. doi: 10.3390/ijms18061233. Int J Mol Sci. 2017. PMID: 28594346 Free PMC article. Review.
-
Analysis of the human replication protein A:Rad52 complex: evidence for crosstalk between RPA32, RPA70, Rad52 and DNA.J Mol Biol. 2002 Aug 2;321(1):133-48. doi: 10.1016/s0022-2836(02)00541-7. J Mol Biol. 2002. PMID: 12139939
Cited by
-
Protein-DNA/RNA Interactions: An Overview of Investigation Methods in the -Omics Era.J Proteome Res. 2021 Jun 4;20(6):3018-3030. doi: 10.1021/acs.jproteome.1c00074. Epub 2021 May 7. J Proteome Res. 2021. PMID: 33961438 Free PMC article. Review.
-
Phosphorylation of Deinococcus radiodurans RecA Regulates Its Activity and May Contribute to Radioresistance.J Biol Chem. 2016 Aug 5;291(32):16672-85. doi: 10.1074/jbc.M116.736389. Epub 2016 Jun 2. J Biol Chem. 2016. PMID: 27255712 Free PMC article.
-
Single-molecule views of protein movement on single-stranded DNA.Annu Rev Biophys. 2012;41:295-319. doi: 10.1146/annurev-biophys-042910-155351. Epub 2012 Feb 23. Annu Rev Biophys. 2012. PMID: 22404684 Free PMC article. Review.
-
Stress-dependent nucleolin mobilization mediated by p53-nucleolin complex formation.Mol Cell Biol. 2002 Aug;22(16):6014-22. doi: 10.1128/MCB.22.16.6014-6022.2002. Mol Cell Biol. 2002. PMID: 12138209 Free PMC article.
-
Bacterial single-stranded DNA-binding proteins are phosphorylated on tyrosine.Nucleic Acids Res. 2006 Mar 20;34(5):1588-96. doi: 10.1093/nar/gkj514. Print 2006. Nucleic Acids Res. 2006. PMID: 16549871 Free PMC article.
Publication types
MeSH terms
Substances
Grants and funding
LinkOut - more resources
Full Text Sources
Other Literature Sources
Research Materials
Miscellaneous