Roles of OB-Fold Proteins in Replication Stress
Dinh-Duc Nguyen, Eugene Y. Kim, Pau Biak Sang, Weihang Chai
Abstract
Accurate DNA replication is essential for maintaining genome stability. However, this stability becomes vulnerable when replication fork progression is stalled or slowed - a condition known as replication stress. Prolonged fork stalling can cause DNA damage, leading to genome instabilities. Thus, cells have developed several pathways and a complex set of proteins to overcome the challenge at stalled replication forks. Oligonucleotide/oligosaccharide binding (OB)-fold containing proteins are a group of proteins that play a crucial role in fork protection and fork restart. These proteins bind to single-stranded DNA with high affinity and prevent premature annealing and unwanted nuclease digestion. Among these OB-fold containing proteins, the best studied in eukaryotic cells are replication protein A (RPA) and breast cancer susceptibility protein 2 (BRCA2). Recently, another RPA-like protein complex CTC1-STN1-TEN1 (CST) complex has been found to counter replication perturbation. In this review, we discuss the latest findings on how these OB-fold containing proteins (RPA, BRCA2, CST) cooperate to safeguard DNA replication and maintain genome stability.