Pcna-KO Mouse

Proliferating cell nuclear antigen (PCNA) is an essential factor in DNA replication and repair [1]. It forms a homotrimeric ring that encircles DNA, acting as a processivity factor for DNA polymerases and a landing platform for various proteins interacting with DNA and chromatin. This multitasking protein is involved in regulating DNA damage repair, chromatin formation during replication, and sister chromatid segregation [3]. The study of PCNA in genetic models is valuable for understanding its functions in these processes.

PCNA is a potential target for cancer treatment. It interacts with a wide range of proteins through the PCNA-interacting protein (PIP) box. Understanding the structure-function relationships of PCNA, especially the sliding mechanism and PIP motif recognition, may offer therapeutic opportunities [1]. Peptide mimetics targeting PCNA could be developed as broad-spectrum cancer therapeutics [2]. Additionally, small molecule PCNA inhibitors like AOH1996 selectively kill cancer cells by enhancing the interaction between PCNA and RPB1, dissociating PCNA from actively transcribed chromatin regions, and inducing DNA double-stranded breaks in a transcription-dependent manner [4].

In conclusion, PCNA is crucial for DNA-related biological processes. Its study in models has revealed its significance in cancer, with potential for developing new cancer therapies. Targeting PCNA's functions in DNA replication and repair through small molecules or peptide mimetics may provide novel strategies for cancer treatment.

References:

1. González-Magaña, Amaia, Blanco, Francisco J. 2020. Human PCNA Structure, Function and Interactions. In Biomolecules, 10, . doi:10.3390/biom10040570. https://pubmed.ncbi.nlm.nih.gov/32276417/

2. Horsfall, Aimee J, Abell, Andrew D, Bruning, John B. 2019. Targeting PCNA with Peptide Mimetics for Therapeutic Purposes. In Chembiochem : a European journal of chemical biology, 21, 442-450. doi:10.1002/cbic.201900275. https://pubmed.ncbi.nlm.nih.gov/31247123/

3. Arbel, Matan, Choudhary, Karan, Tfilin, Ofri, Kupiec, Martin. 2021. PCNA Loaders and Unloaders-One Ring That Rules Them All. In Genes, 12, . doi:10.3390/genes12111812. https://pubmed.ncbi.nlm.nih.gov/34828416/

4. Gu, Long, Li, Min, Li, Caroline M, Perry, J Jefferson P, Malkas, Linda H. 2023. Small molecule targeting of transcription-replication conflict for selective chemotherapy. In Cell chemical biology, 30, 1235-1247.e6. doi:10.1016/j.chembiol.2023.07.001. https://pubmed.ncbi.nlm.nih.gov/37531956/