C57BL/6JCya-Pole3em1flox/Cya
Common Name
Pole3-flox
Product ID
S-CKO-12465
Backgroud
C57BL/6JCya
Strain ID
CKOCMP-59001-Pole3-B6J-VA
When using this mouse strain in a publication, please cite “Pole3-flox Mouse (Catalog S-CKO-12465) were purchased from Cyagen.”
Product Type
Age
Genotype
Sex
Quantity
Basic Information
Strain Name
Pole3-flox
Strain ID
CKOCMP-59001-Pole3-B6J-VA
Gene Name
Product ID
S-CKO-12465
Gene Alias
1810034K18Rik, YBL1
Background
C57BL/6JCya
NCBI ID
Modification
Conditional knockout
Chromosome
Chr 4
Phenotype
Datasheet
Application
--
Strain Description
Ensembl Number
ENSMUST00000030091
NCBI RefSeq
NM_021498
Target Region
Exon 1~4
Size of Effective Region
~2.5 kb
Overview of Gene Research
POLE3, also known as DPB4/YBL1/CHRAC17, is a subunit of DNA polymerase epsilon. It contains a histone-like domain and is involved in multiple essential biological functions. POLE3 is crucial for processes like DNA replication, chromatin integrity maintenance, and is associated with pathways related to histone modification and DNA damage repair [5,6]. Its biological importance extends to maintaining genomic stability and cell-type-specific functions, with implications in development and disease [7]. Genetic models, such as knockout mouse models, are valuable for studying POLE3's functions.
Loss-of-function experiments have revealed multiple key roles of POLE3. In HIV-1 replication, knockdown and knockout experiments showed that POLE3 is a transcriptional repressor of unintegrated HIV-1 DNA. It maintains unintegrated HIV-1 DNA in a repressive chromatin state, affecting virus integration efficiency and escape from innate immune sensing [1]. In cancer research, loss of POLE3-POLE4 complex sensitizes cancer cells to PARP inhibitors. This is not due to homologous recombination defects but rather triggers replicative gap accumulation in a PRIMPOL-dependent manner [2,4]. Also, POLE3 is involved in DNA double-strand breaks repair. WDR70 promotes H2BK120ub1, and deposition of related histone modifications in POLE3 loci is sensitive to its transcription. POLE3 interacts with CHRAC1 to promote DNA repair, and a CHRAC1 mutation in colorectal cancer leads to DNA repair defects [3].
In conclusion, POLE3 plays essential roles in DNA-related biological processes, including replication, repair, and chromatin-associated functions. Model-based research, especially KO/CKO mouse models, has provided insights into its functions in diseases such as viral infections and cancer. Understanding POLE3 can potentially contribute to developing new strategies for treating these diseases.
References：
1. Thenin-Houssier, Suzie, Machida, Shinichi, Jahan, Cyprien, Cuvier, Olivier, Benkirane, Monsef. 2023. POLE3 is a repressor of unintegrated HIV-1 DNA required for efficient virus integration and escape from innate immune sensing. In Science advances, 9, eadh3642. doi:10.1126/sciadv.adh3642. https://pubmed.ncbi.nlm.nih.gov/37922361/
2. Hill, Bethany Rebekah, Ozgencil, Meryem, Buckley-Benbow, Lauryn, Agnarelli, Alessandro, Bellelli, Roberto. 2024. Loss of POLE3-POLE4 unleashes replicative gap accumulation upon treatment with PARP inhibitors. In Cell reports, 43, 114205. doi:10.1016/j.celrep.2024.114205. https://pubmed.ncbi.nlm.nih.gov/38753485/
3. Mao, Xiaobing, Wu, Jian, Zhang, Qin, Liu, Cong, Han, Junhong. 2023. Requirement of WDR70 for POLE3-mediated DNA double-strand breaks repair. In Science advances, 9, eadh2358. doi:10.1126/sciadv.adh2358. https://pubmed.ncbi.nlm.nih.gov/37682991/
4. Mamar, Hasan, Fajka-Boja, Roberta, Mórocz, Mónika, Huet, Sébastien, Timinszky, Gyula. . The loss of DNA polymerase epsilon accessory subunits POLE3-POLE4 leads to BRCA1-independent PARP inhibitor sensitivity. In Nucleic acids research, 52, 6994-7011. doi:10.1093/nar/gkae439. https://pubmed.ncbi.nlm.nih.gov/38828775/
5. Bellelli, Roberto, Belan, Ondrej, Pye, Valerie E, Almouzni, Genevieve, Boulton, Simon J. 2018. POLE3-POLE4 Is a Histone H3-H4 Chaperone that Maintains Chromatin Integrity during DNA Replication. In Molecular cell, 72, 112-126.e5. doi:10.1016/j.molcel.2018.08.043. https://pubmed.ncbi.nlm.nih.gov/30217558/
6. Bolognese, Fabrizio, Forni, Claudia, Caretti, Giuseppina, Minuzzo, Mario, Mantovani, Roberto. 2006. The Pole3 bidirectional unit is regulated by MYC and E2Fs. In Gene, 366, 109-16. doi:. https://pubmed.ncbi.nlm.nih.gov/16403426/
7. Siamishi, Iliana, Iwanami, Norimasa, Clapes, Thomas, O'Meara, Connor P, Boehm, Thomas. . Lymphocyte-Specific Function of the DNA Polymerase Epsilon Subunit Pole3 Revealed by Neomorphic Alleles. In Cell reports, 31, 107756. doi:10.1016/j.celrep.2020.107756. https://pubmed.ncbi.nlm.nih.gov/32553171/
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
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