Nguyen Dinh-Duc, Kim Eugene Y, Sang Pau Biak, Chai Weihang
Department of Cancer Biology, Cardinal Bernardin Cancer Center, Loyola University Chicago Stritch School of Medicine, Maywood, IL, United States.
Front Cell Dev Biol. 2020 Sep 11;8:574466. doi: 10.3389/fcell.2020.574466. eCollection 2020.
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.
准确的DNA复制对于维持基因组稳定性至关重要。然而，当复制叉前进受阻或减慢时——这种情况被称为复制应激，这种稳定性就会变得脆弱。长时间的复制叉停滞会导致DNA损伤，进而导致基因组不稳定。因此，细胞已经发展出几种途径和一套复杂的蛋白质来应对复制叉停滞带来的挑战。含寡核苷酸/寡糖结合（OB）折叠的蛋白质是一类在复制叉保护和重新启动中起关键作用的蛋白质。这些蛋白质以高亲和力结合单链DNA，防止过早退火和不必要的核酸酶消化。在这些含OB折叠的蛋白质中，在真核细胞中研究得最深入的是复制蛋白A（RPA）和乳腺癌易感蛋白2（BRCA2）。最近，另一种类似RPA的蛋白质复合物CTC1-STN1-TEN1（CST）复合物被发现可应对复制干扰。在这篇综述中，我们讨论了关于这些含OB折叠的蛋白质（RPA、BRCA2、CST）如何协同保护DNA复制并维持基因组稳定性的最新发现。
