The post translational modification of key regulators of ATR signaling in DNA replication

Abstract

DNA replication is one of the most critical psychological process, which mainly consists of three steps: initiation, elongation, and termination. Precise regulation through all stages of DNA replication is essential for maintaining genome integrity in proliferating cells. During each cell cycle, the complete genetic information existing in the DNA needs to be duplicated and passed on to the daughter cells. The DNA replication machinery is confronted with many challenges and stresses owing to endogenous and exogenous facts that could harm the faithful duplication of the DNA. The abnormality of DNA replication could cause genomic instability and tumorigenesis. ATR is a master regulator of cells in response to DNA replication stress to safeguard genomic stability and prevent tumorigenesis. In the past years, the key functions of post-translational modification (PTM) in ATR signaling transduction has been explored. ATR signaling is complicatedly and tightly regulated by multiple PTMs, such as phosphorylation, acetylation, ubiquitination, SUMOylation and so on. Here, we summarize how the ATR signaling pathway is tightly regulated by PTM. Furthermore, we describe the critical roles of ATR signaling in DNA replication and safeguarding genomic stability. In the past years, the key functions of post-translational modification (PTM) in DNA replication has been explored. These findings benefit for us better understand the complicated mechanism of DNA replication signaling pathway.

Exploring SPK98 for the Selective Sensitization of ATM- or P53-Deficient Cancer Cells

“…To perform ATR enzyme inhibition studies with SPK98 (Figure A), the FLAG-ATR was expressed and purified from HEK293T cells. Since ATR requires multiple PTMs and protein partners to achieve its optimal kinase activity, the cells were exposed to UV-C before proceeding with purification. UV-C treatment has been reported to significantly enhance the level of active ATR in cells. , This knowledge was used to increase the yield of active protein during purification.…”

Comparative Phosphoproteomics of Neuro-2a Cells under Insulin Resistance Reveals New Molecular Signatures of Alzheimer’s Disease

“…Protein phosphorylation plays a key role in cell signaling, gene expression, and differentiation [62,63]. It is also involved in the global control of DNA replication during the cell cycle and in mechanisms that cope with stress-induced replication blocks [64]. Kinases catalyze protein phosphorylation by attaching phosphate groups to specific amino acids [65,66].…”