Eukaryotic Replication Protein A

Abstract

Replication protein A ( RPA ) is a single‐stranded deoxyribonucleic acid (DNA)‐binding protein required for cellular DNA metabolism. RPA is a heterotrimeric complex composed of 70, 32 and 14 kDa subunits, commonly referred to as RPA1 , RPA2 and RPA3 . Homologous complexes are found in all eukaryotes. RPA binds single‐stranded DNA with high‐affinity and low‐sequence specificity. In addition, RPA interacts specifically with, and modulates the activity of, many proteins required for DNA metabolism in cells. RPA primarily functions in the cell to stabilize single‐stranded DNA. RPA activity is essential for DNA replication, DNA repair and recombination. In addition, RPA is involved in the cellular DNA damage response. Disruption of RPA activity or of the activity of RPA ‐interacting proteins is associated with many human diseases, including cancer. Key Concepts: Replication protein A (RPA) is the major eukaryotic single‐stranded DNA‐binding protein. RPA is a heterotrimeric protein complex with a flexible structure; each subunit is composed of one or more DNA‐binding domains that are linked or flanked by flexible linkers and regulatory regions. RPA participates in many cellular processes essential for life, including DNA replication and repair by binding to single‐stranded DNA intermediates and interacting with proteins required for these processes.