C57BL/6JCya-Primpolem1/Cya
Common Name:
Primpol-KO
Product ID:
S-KO-17079
Background:
C57BL/6JCya
Product Type
Age
Genotype
Sex
Quantity
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Basic Information
Strain Name
Primpol-KO
Strain ID
KOCMP-408022-Primpol-B6J-VB
Gene Name
Product ID
S-KO-17079
Gene Alias
Ccdc111
Background
C57BL/6JCya
NCBI ID
Modification
Conventional knockout
Chromosome
8
Phenotype
Document
Application
--
Note: When using this mouse strain in a publication, please cite “C57BL/6JCya-Primpolem1/Cya mice (Catalog S-KO-17079) were purchased from Cyagen.”
Strain Description
Ensembl Number
ENSMUST00000211400
NCBI RefSeq
NM_001001184
Target Region
Exon 4
Size of Effective Region
~0.6 kb
Detailed Document
Overview of Gene Research
Primpol, also known as Primase and DNA-directed Polymerase, is an enzyme with both primase and polymerase activities. It is a key player in DNA damage tolerance pathways, allowing DNA replication to continue when forks are challenged by DNA lesions induced by endogenous and exogenous sources. This is crucial for the timely and faithful duplication of the genome in vertebrate and human cells [1,2,4,5,6].
PRIMPOL repriming enables DNA replication to skip DNA lesions, leading to ssDNA gaps. These gaps are filled through temporally distinct post-replicative repair mechanisms during different phases of the cell cycle. For example, in G2, a mechanism dependent on RAD18, PCNA monoubiquitination, and REV1 and POLζ translesion synthesis polymerases promotes gap filling, while in S phase, the E2-conjugating enzyme UBC13, the RAD51 recombinase, and REV1-POLζ are responsible [3]. Also, under oncogenic KRAS-induced replication stress, PrimPol is phosphorylated at Ser255 and promotes repriming to maintain fork progression and cell survival in an ATR/Chk1-dependent manner, though it generates ssDNA gaps at heterochromatin leading to genomic instability [7]. Genome-wide Nuclease technology screens show that PRIMPOL is needed for cell survival following loss of Y-family polymerases REV1 and POLη in a lesion-dependent manner and promotes survival of cells lacking PCNA K164-dependent post-replicative gap filling [8].
In conclusion, Primpol is essential for DNA damage tolerance, facilitating replication fork progression during stress. Studies on Primpol's role in DNA replication and repair mechanisms, especially through model-based research like genome-wide screens, help us understand its contribution to genome stability and cell survival. The findings related to its function in oncogenic KRAS-induced stress also suggest its potential importance in cancer-related disease areas [3,7,8].
References:
1. Tirman, Stephanie, Cybulla, Emily, Quinet, Annabel, Meroni, Alice, Vindigni, Alessandro. 2020. PRIMPOL ready, set, reprime! In Critical reviews in biochemistry and molecular biology, 56, 17-30. doi:10.1080/10409238.2020.1841089. https://pubmed.ncbi.nlm.nih.gov/33179522/
2. Díaz-Talavera, Alberto, Montero-Conde, Cristina, Leandro-García, Luis Javier, Robledo, Mercedes. 2022. PrimPol: A Breakthrough among DNA Replication Enzymes and a Potential New Target for Cancer Therapy. In Biomolecules, 12, . doi:10.3390/biom12020248. https://pubmed.ncbi.nlm.nih.gov/35204749/
3. Tirman, Stephanie, Quinet, Annabel, Wood, Matthew, Zou, Lee, Vindigni, Alessandro. . Temporally distinct post-replicative repair mechanisms fill PRIMPOL-dependent ssDNA gaps in human cells. In Molecular cell, 81, 4026-4040.e8. doi:10.1016/j.molcel.2021.09.013. https://pubmed.ncbi.nlm.nih.gov/34624216/
4. Guilliam, Thomas A, Doherty, Aidan J. 2017. PrimPol-Prime Time to Reprime. In Genes, 8, . doi:10.3390/genes8010020. https://pubmed.ncbi.nlm.nih.gov/28067825/
5. Boldinova, Elizaveta O, Makarova, Alena V. . Regulation of Human DNA Primase-Polymerase PrimPol. In Biochemistry. Biokhimiia, 88, 1139-1155. doi:10.1134/S0006297923080084. https://pubmed.ncbi.nlm.nih.gov/37758313/
6. Bailey, Laura J, Doherty, Aidan J. . Mitochondrial DNA replication: a PrimPol perspective. In Biochemical Society transactions, 45, 513-529. doi:10.1042/BST20160162. https://pubmed.ncbi.nlm.nih.gov/28408491/
7. Igarashi, Taichi, Mazevet, Marianne, Yasuhara, Takaaki, Zou, Lee, Shiotani, Bunsyo. 2023. An ATR-PrimPol pathway confers tolerance to oncogenic KRAS-induced and heterochromatin-associated replication stress. In Nature communications, 14, 4991. doi:10.1038/s41467-023-40578-2. https://pubmed.ncbi.nlm.nih.gov/37591859/
8. Mellor, Christopher, Nassar, Joelle, Šviković, Saša, Sale, Julian E. . PRIMPOL ensures robust handoff between on-the-fly and post-replicative DNA lesion bypass. In Nucleic acids research, 52, 243-258. doi:10.1093/nar/gkad1054. https://pubmed.ncbi.nlm.nih.gov/37971291/
Quality Control Standard
Sperm Test
Pre-cryopreservation: Measurement of sperm concentration, determination of sperm viability.
Post-cryopreservation: A vial of cryopreserved sperms is selected for in-vitro fertilization from each batch.
Environmental Standards:SPF
Available Region:Global
Source:Cyagen