Poldip3, also known as DNA polymerase delta interacting protein 3, was initially identified as a DNA polymerase δ (Pol δ) interacting protein. It is involved in various RNA and DNA related cellular processes, such as transcription, pre-mRNA splicing, mRNA export, translation, genome-wide R-loop disassembly, and DNA damage checkpoint activation. It belongs to the polymerase δ-interacting protein family and is associated with multiple biological pathways related to cell growth, repair, and viral defense [1,4].

Gene knockout (KO) of Poldip3 in cells reveals its crucial roles. POLDIP3-KO cells show sensitivity to replication fork blockers, indicating its importance in DNA replication under stress [5]. In the context of coronavirus infection, POLDIP3 knockout by CRISPR-Cas9 editing significantly promotes porcine deltacoronavirus (PDCoV) infection, suggesting it serves as an antiviral regulator against PDCoV [2]. In addition, loss of RTEL1 and Poldip3 in human cell culture models leads to marked R-loop accumulation at active replication sites, enhancing endogenous replication stress and genomic instability, showing their shared role in DNA replication control under stress [3].

In summary, Poldip3 is essential for maintaining genomic stability during DNA replication and in the host antiviral response. Studies using gene knockout models have revealed its significance in these biological processes, particularly in relation to viral infections and DNA replication-associated stress. These findings contribute to understanding the underlying mechanisms of related diseases and may provide potential therapeutic targets [2,3,5].

References:

1. Singh, Manrose, Zhang, Sufang, Perez, Alexis M, Lee, Marietta Y W T, Zhang, Dong. 2022. POLDIP3: At the Crossroad of RNA and DNA Metabolism. In Genes, 13, . doi:10.3390/genes13111921. https://pubmed.ncbi.nlm.nih.gov/36360158/

2. Wu, Yang, Li, Mingwei, Tian, Jin, Guo, Longjun, Feng, Li. 2023. Broad antagonism of coronaviruses nsp5 to evade the host antiviral responses by cleaving POLDIP3. In PLoS pathogens, 19, e1011702. doi:10.1371/journal.ppat.1011702. https://pubmed.ncbi.nlm.nih.gov/37801439/

3. Björkman, Andrea, Johansen, Søren L, Lin, Lin, Bartek, Jiri, Schou, Kenneth B. 2020. Human RTEL1 associates with Poldip3 to facilitate responses to replication stress and R-loop resolution. In Genes & development, 34, 1065-1074. doi:10.1101/gad.330050.119. https://pubmed.ncbi.nlm.nih.gov/32561545/

4. Huang, Peiluo, Wu, Lei, Zhu, Ningxia, Zhao, Hongtao, Du, Juan. 2022. The polymerase δ-interacting protein family and their emerging roles in diseases. In Frontiers in medicine, 9, 1026931. doi:10.3389/fmed.2022.1026931. https://pubmed.ncbi.nlm.nih.gov/36425112/

5. Zhang, Sufang, Lee, Ernest Y C, Lee, Marietta Y W T, Zhang, Dong. 2022. DNA polymerase delta interacting protein 3 facilitates the activation and maintenance of DNA damage checkpoint in response to replication stress. In Animal models and experimental medicine, 5, 461-469. doi:10.1002/ame2.12274. https://pubmed.ncbi.nlm.nih.gov/36168146/