POLE3 Recombinant Protein
- Known as:
- POLE3 Recombinant Protein
- Catalog number:
- XW-RP3196
- Product Quantity:
- 0.1 mg
- Category:
- -
- Supplier:
- Prosci
- Gene target:
- POLE3 Recombinant Protein
Related genes to: POLE3 Recombinant Protein
- Gene:
- POLE3 NIH gene
- Name:
- DNA polymerase epsilon 3, accessory subunit
- Previous symbol:
- -
- Synonyms:
- CHRAC17, Ybl1, p17, CHARAC17, CHRAC2
- Chromosome:
- 9q32
- Locus Type:
- gene with protein product
- Date approved:
- 2001-09-21
- Date modifiied:
- 2018-07-11
Related products to: POLE3 Recombinant Protein
Related articles to: POLE3 Recombinant Protein
- Cisplatin (DDP) is a key chemotherapeutic agent for pancreatic cancer (PC), but its efficacy is often limited by the development of DNA damage repair (DDR)-mediated resistance. Ubiquitin-specific peptidase 15 (USP15) is known to activate DDR pathways; however, its specific role and clinical relevance in PC remain poorly understood. We analyzed USP15 expression and its clinical significance using public databases, tissue microarrays, and cell lines through RT-qPCR, Western blot, and immunohistochemistry. The effect of USP15 on DDP resistance was evaluated using colony formation and flow cytometry assays. Protein interaction between USP15 and POLE3 was confirmed by Co-IP. DNA damage levels were assessed via immunofluorescence staining, neutral comet assays, and host cell reactivation. Both loss-of-function and gain-of-function studies of USP15 were conducted in a mouse xenograft model. We found that USP15 was significantly upregulated in PC tissues and correlated with poor patient prognosis. Overexpression of USP15 enhanced DDP resistance in PC cells in vitro and in vivo. Enrichment analysis indicated a strong association between USP15 expression and DDR-related genes. Mechanistically, USP15 was found to bind to POLE3 and suppress its ubiquitination-dependent degradation, thereby facilitating DDP-induced DNA damage repair. Our findings highlight the upregulation and prognostic value of USP15 in PC, and uncover its role in promoting DDR-mediated DDP resistance through stabilization of POLE3. - Source: PubMed
Publication date: 2026/04/08
Ma ZhigangLi HengzhenZeng GuangchunJiao GuangtaoHan ShulingRuan YuliLan YaGuan XinSong YushuaiLiu ChaoLu XiaolinLi Zhiwei - The maintenance of genome stability requires efficient leading strand synthesis by DNA Polymerase Epsilon (Polε). By performing CRISPR genetic screens in cells lacking the POLE4 subunit of Polε we define a genetic map of the factors required to support Polε function in the absence of its accessory subunits. A set of genes involved in iron metabolism emerge as required to sustain Iron Sulphur Cluster (ISC)-dependent Polε activity. We then dissect a synthetic lethal interaction between POLE3-POLE4 and the CHTF18-RFC2/5 complex. By combining cell biology, structural modelling and biochemistry, we define the existence of two tiers of regulation of Polε processivity: leading strand-specific loading of PCNA by CHTF18-RFC2/5 and "gripping" of newly synthesised dsDNA by POLE3-POLE4. The combined loss of these functions is incompatible with leading strand synthesis and viability. In summary, we describe the biochemical basis of human leading strand synthesis and the consequence of its dysfunction in genome stability. - Source: PubMed
Publication date: 2025/12/04
Agnarelli AlessandroBuckley-Benbow LaurynOzgencil MeryemLad MelanieAmpah Khamal KwesiKalinka AlexBelan OndrejMaslen SarahSkehel Mark JWalter DavidDay MatthewBellelli Roberto - In mammalian cells, MCM2 and POLE3/4 safeguard the symmetrical segregation of parental histones to the leading and lagging strands of newly synthesized DNA. However, the identity of additional proteins involved in parental histone distribution remains elusive. We used TurboID proximity labeling to identify interaction partners of MCM2 and POLE3/4 in mouse cells. This approach provided a candidate protein library potentially involved in the MCM2 and POLE3/POLE4-mediated process of parental histone segregation. DNA polymerase δ subunit 3 (POLD3) was a protein whose intensity differed between the interactomes of wild-type MCM2 and its histone-binding mutant. We showed POLD3 bound to both MCM2 and the histone (H3-H4) tetramers. Moreover, MCM2's histone binding affected interactions between POLD3 and histone H3. More importantly, POLD3 was required for the symmetrical transfer of parental histones H3-H4 to the leading and lagging strands of newly synthesized DNA in mouse cells. In short, our findings establish that POLD3 forms a protein complex with MCM2 and histone (H3-H4) tetramers, functioning as a novel histone chaperone to regulate parental histone segregation in mammalian cells. - Source: PubMed
Publication date: 2025/11/27
Sun YapingLiang XiaoyanLiu FangZhao WenjuanZhou JiaqiLi YueYao YuanZhang ZiweiLi GangChan KuimingZhang DaoqinWang ZhiquanGao YuanYu ChuanheWu YuchunKang XingQiu LingyuLi NanGan Haiyun - The growing need for effective HBV treatments and lead compounds with novel mechanisms prompted us to explore synthetic strategies for generating skeletally diverse alkaloidal Michael acceptors. Our approach uniquely embeds Michael acceptors directly within multicyclic alkaloid-inspired frameworks, exploiting the azepinoindole scaffold-a privileged structure in indole alkaloids. A single-step assembly between the versatile intermediate 13 with methyl propiolate 14 or its derivatives enabled the rapid and divergent synthesis of six alkaloidal Michael acceptors (15-20). This strategy facilitated systematic diversification of three-dimensional functional group arrangements and precise tuning of the electronic and steric properties of the embedded α,β-unsaturated carbonyl moieties. The optimal hit 15 inhibited hepatitis B surface antigen (HBsAg) production with an IC of 2.48 μM and significantly reduced levels of covalently closed circular DNA (cccDNA), the master template of HBV. Unlike existing nucleoside/nucleotide-based anti-HBV drugs that primarily inhibit reverse transcription, the alkaloidal Michael acceptor 15 suppressed both cccDNA and relaxed circular DNA (rcDNA) levels, suggesting a potential pathway toward a functional HBV cure. Our study also streamlined the target identification by leveraging the covalent binding properties of the Michael acceptors and the operational simplicity of biotin- or fluorescent-tag attachment a pre-installed alkyne moiety. Competitive pull-down experiments identified several potential target proteins, involving DNA polymerase epsilon subunit 3 (POLE3). Notably, the alkaloidal Michael acceptor 15 was demonstrated to covalently modify Cys51 in POLE3, providing new insights into virus-host interactions and opening novel avenues for targeted anti-HBV therapies. This approach represents a significant advance beyond traditional screening methods and underscores the potential of skeletally diverse alkaloidal Michael acceptors in antiviral drug development. - Source: PubMed
Publication date: 2025/10/21
Kaneko NobutoHimeno MisaoKobayashi YuhiTanifuji RyoKubota HirokiMizoguchi HarukiMuroi MakotoSuzuki TakehiroSugiyama MasayaDohmae NaoshiOsada HiroyukiKido TaketomoMiyajima AtsushiOguri Hiroki - Replication timing (RT), the temporal order of DNA replication during S phase, influences regional mutation rates, yet the mechanistic basis for RT-associated mutagenesis remains incompletely defined. To identify drivers of RT-dependent mutation biases, we analyzed whole-genome sequencing data from cells with disruptions in DNA replication/repair genes or exposed to mutagenic compounds. Mutation distributions between early- and late-replicating regions were compared using bootstrapping and statistical modeling. We identified 14 genes that exhibit differential effects in early- or late-replicating regions, encompassing multiple DNA repair pathways, including mismatch repair (, and ), trans-lesion DNA synthesis () and double-strand break repair ( and ), DNA polymerases ( and ), and other genes central to genomic instability ( and ). Similar analyses of mutagenic compounds revealed 19 compounds with differential effects on replication timing. These results establish replication timing as a critical modulator of mutagenesis, with distinct DNA repair pathways and exogenous agents exhibiting replication timing-specific effects on genomic instability. Our systematic bioinformatics approach identifies new DNA repair genes and mutagens that exhibit differential activity during the S phase. These findings pave the way for further investigation of factors that contribute to genome instability during cancer transformation. - Source: PubMed
Publication date: 2025/07/29
Gross-Samuels HadasKoren AmnonSimon Itamar