Nasheuer, H.P.; Meaney, A.M.; Hulshoff, T.; Thiele, I.; Onwubiko, N.O. Replication Protein A, the Main Eukaryotic Single-Stranded DNA Binding Protein, a Focal Point in Cellular DNA Metabolism. Int. J. Mol. Sci.2024, 25, 588.
Nasheuer, H.P.; Meaney, A.M.; Hulshoff, T.; Thiele, I.; Onwubiko, N.O. Replication Protein A, the Main Eukaryotic Single-Stranded DNA Binding Protein, a Focal Point in Cellular DNA Metabolism. Int. J. Mol. Sci. 2024, 25, 588.
Nasheuer, H.P.; Meaney, A.M.; Hulshoff, T.; Thiele, I.; Onwubiko, N.O. Replication Protein A, the Main Eukaryotic Single-Stranded DNA Binding Protein, a Focal Point in Cellular DNA Metabolism. Int. J. Mol. Sci.2024, 25, 588.
Nasheuer, H.P.; Meaney, A.M.; Hulshoff, T.; Thiele, I.; Onwubiko, N.O. Replication Protein A, the Main Eukaryotic Single-Stranded DNA Binding Protein, a Focal Point in Cellular DNA Metabolism. Int. J. Mol. Sci. 2024, 25, 588.
Abstract
Replication protein A (RPA) is a heterotrimeric protein complex and the main single-stranded DNA (ssDNA) binding protein in eukaryotes. RPA has key functions in most of the DNA-associated metabolic pathways and DNA damage signalling. Its high affinity for ssDNA helps to stabilise ssDNA structures and prevents the DNA sequence from nuclease attacks. RPA consists of multiple DNA-binding domains which are oligonucleotide/oligosaccharide-binding (OB)-folds, responsible for DNA binding, and interactions with proteins. These RPA-ssDNA and RPA-protein interactions are crucial for DNA replication, DNA repair, DNA damage signalling, and the conversation of the genetic information of cells. Proteins such as ATR use RPA to locate to regions of DNA damage for DNA damage signalling. Recruitment of nucleases and DNA exchange factors to sites of double strand breaks are also an important RPA function to ensure effective DNA recombination to correct these DNA lesions. Due to its high affinity to ssDNA, RPA’s removal from ssDNA is of central importance to allow these metabolic pathway to proceed and processes to exchange RPA against downstream factors are established in all eukaryotes. These facetted and multi-layered functions of RPA will be discussed in detail in the review. RPA is also a major player in a variety of human diseases, which will be discussed.
Keywords
DNA Replication; DNA repair; homologous recombination; DNA damage signalling; replication protein A, DNA binding; protein interactions
Subject
Biology and Life Sciences, Biochemistry and Molecular Biology
Copyright:
This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
