关于人类单链DNA结合蛋白1（hSSB1，OBFC2B）在DNA修复中功能调控的结构视角
A Structural Perspective on the Regulation of Human Single-Stranded DNA Binding Protein 1 (hSSB1, OBFC2B) Function in DNA Repair.
作者信息
Lawson Teegan, El-Kamand Serene, Kariawasam Ruvini, Richard Derek J, Cubeddu Liza, Gamsjaeger Roland
机构信息
School of Science and Health, Western Sydney University, Sydney, Locked Bag 1797, Penrith, NSW 2751, Australia.
Genome Stability Laboratory, Cancer and Ageing Research Program, Institute of Health and Biomedical Innovation, Translational Research Institute, Queensland University of Technology, Woolloongabba, Queensland 4102, Australia.
出版信息
Comput Struct Biotechnol J. 2019 Mar 28;17:441-446. doi: 10.1016/j.csbj.2019.03.014. eCollection 2019.
Single-stranded DNA binding (SSB) proteins are essential to protect singe-stranded DNA (ssDNA) that exists as a result of several important DNA repair pathways in living cells. In humans, besides the well-characterised Replication Protein A (RPA) we have described another SSB termed human SSB1 (hSSB1, OBFC2B) and have shown that this protein is an important player in the maintenance of the genome. In this review we define the structural and biophysical details of how hSSB1 interacts with both DNA and other essential proteins. While the presence of the oligonucleotide/oligosaccharide (OB) domain ensures ssDNA binding by hSSB1, it has also been shown to self-oligomerise as well as interact with and being modified by several proteins highlighting the versatility that hSSB1 displays in the context of DNA repair. A detailed structural understanding of these processes will likely lead to the designs of tailored hSSB1 inhibitors as anti-cancer drugs in the near future.
单链DNA结合（SSB）蛋白对于保护活细胞中因多种重要DNA修复途径而产生的单链DNA（ssDNA）至关重要。在人类中，除了已被充分表征的复制蛋白A（RPA）外，我们还描述了另一种SSB，称为人类SSB1（hSSB1，OBFC2B），并表明该蛋白在基因组维持中起着重要作用。在这篇综述中，我们阐述了hSSB1如何与DNA和其他必需蛋白相互作用的结构和生物物理细节。虽然寡核苷酸/寡糖（OB）结构域的存在确保了hSSB1与ssDNA的结合，但它也已被证明会自我寡聚，以及与多种蛋白质相互作用并被其修饰，这突出了hSSB1在DNA修复过程中所展现的多功能性。对这些过程的详细结构理解可能会在不久的将来促成设计出作为抗癌药物的定制化hSSB1抑制剂。
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