ATAD5
- Known as:
- ATAD5
- Catalog number:
- 002113A
- Product Quantity:
- 250ul
- Category:
- -
- Supplier:
- ABM
- Gene target:
- ATAD5
Related genes to: ATAD5
- Gene:
- ATAD5 NIH gene
- Name:
- ATPase family AAA domain containing 5
- Previous symbol:
- C17orf41
- Synonyms:
- FLJ12735, FRAG1, ELG1
- Chromosome:
- 17q11.2
- Locus Type:
- gene with protein product
- Date approved:
- 2005-05-24
- Date modifiied:
- 2019-01-18
Related products to: ATAD5
Related articles to: ATAD5
- Replication forks encounter problems during genome duplication that trigger replication stress. Fork reversal is a key stress tolerance pathway that helps mitigate replication challenges to facilitate DNA synthesis. Here, we report the function of origin licensing factor CDT1 in fork remodeling by replication fork reversal. Characterization of replication dynamics during early stages of origin reactivation revealed that CDT1 blocks fork progression without inducing DNA breaks. Notably, CDT1 mediates replication fork reversal under conditions of re-replication and genotoxic stress exposure, and this function is dependent on the interaction with the CMG helicase. Although proliferating cell nuclear antigen (PCNA) sequesters CDT1 for proteolytic degradation under unperturbed conditions, ATAD5-mediated PCNA unloading at stressed forks releases CDT1 to interact with the CMG helicase and promote fork remodeling. Thus, contrary to the notion that CDT1 function must be inactivated in the S phase, our findings uncover a regulatory mechanism that facilitates fork remodeling function of CDT1 in response to replication stress. - Source: PubMed
Publication date: 2026/08/12
Hathaway CaitlinLe ThanhHatoyama YukiKanemaki MasatoDungrawala Huzefa - DNA sliding clamps, including PCNA (proliferating cell nuclear antigen) and the 9-1-1 (RAD9-RAD1-HUS1 in humans) complex, are ring-shaped protein complexes that encircle DNA and serve as central interaction platforms in DNA replication, repair, and checkpoint signaling. While clamp loading at canonical primer-template junctions by AAA+ (ATPases associated with diverse cellular activities) clamp loaders is well established, how clamps are loaded onto physiologically relevant but geometrically constrained DNA intermediates, such as nicks and single-stranded gaps, has remained unclear. Recent cryo-electron microscopy studies reveal that clamp loaders have evolved distinct strategies to overcome these constraints and to specialize for different genomic contexts. At gapped DNA, the eukaryotic clamp loader RFC (replication factor C) engages both 3'- and 5'-recessed DNA ends and can locally unwind DNA, enabling PCNA loading across a wide range of gap sizes. In contrast, the bacterial DnaX clamp loader lacks a 5'-DNA-binding site and does not unwind DNA, instead loading the β-clamp at small gaps (<6 nt) by sharply bending DNA. The checkpoint clamp loader Rad24-RFC (RAD17-RFC in humans) similarly lacks DNA unwinding activity, restricting loading of 9-1-1 clamp to larger gaps (≥6 nt). In a distinct specialization, Ctf18-RFC interacts with the leading-strand DNA polymerase ε, positioning it as a dedicated loader for leading-strand synthesis, whereas Elg1-RFC (ATAD5-RFC in humans) excludes DNA from its chamber and functions as a PCNA unloader. Together, these mechanisms illustrate how clamp loaders are diversified to accommodate DNA structure and replisome context, ensuring coordinated control of genome replication and maintenance. - Source: PubMed
Publication date: 2026/08/10
Zheng FengweiO'Donnell Michael ELi Huilin - Molecular fingerprints and physicochemical descriptors encode complementary structural information, yet most Tox21 benchmarks evaluate only one representation at a time. This study examined whether integrating both closes the reported gap between classical and graph-based deep learning. - Source: PubMed
Publication date: 2026/07/25
Agboola Oluwaseun EAgboola Samuel SAdegbuyi Adekunle TAyinla Zainab A - Hepatocellular carcinoma (HCC) remains a lethal malignancy with limited therapeutic options in advanced disease, highlighting the need to identify selective cytotoxic agents and biologically relevant molecular targets for early anticancer drug discovery. In this study, a focused in-house compound set was screened against HepG2, MCF-7, and MDA-MB-231 cancer cell lines using the MTT assay to identify compounds with selective activity toward HCC-derived cells. The most active hit, HTS00019, was then subjected to an integrated computational target-deconvolution workflow comprising SEA target prediction, reverse docking against cancer-relevant proteins, binding-mode analysis, 100 ns molecular dynamics simulations, MM-GBSA binding free energy estimation, and toxicological profiling using ProTox-3.0. HTS00019 showed potent and selective cytotoxicity toward HepG2 cells, with an IC value of 1.70 ± 0.22 µM and approximately 50-fold selectivity over MCF-7 and MDA-MB-231 cells. SEA and reverse docking analyses prioritized GST-family proteins and TRAP1 as likely candidate targets. Docking suggested favorable binding within the GSTP1 H-site and the ATP-associated region of TRAP1, while molecular dynamics simulations supported stable accommodation of the compound in both proteins, with stronger ligand positional stability in TRAP1. MM-GBSA analysis further favored TRAP1 binding, with a calculated Δ of -75.49 kcal mol compared with -59.98 kcal mol for GSTP1. Interaction analysis indicated hydrophobic and ionic contacts in GSTP1, whereas halogen bonding, π-cation, and hydrophobic interactions contributed to the predicted TRAP1 binding mode. toxicological profiling classified HTS00019 as oral toxicity class 4 and flagged potential hepatotoxicity, mutagenicity, immunotoxicity, and carcinogenicity liabilities, while p53- and ATAD5-related stress pathway predictions were inactive. Overall, HTS00019 was identified as a selective HepG2 cytotoxic hit, with GSTP1 and TRAP1 emerging as computationally prioritized candidate targets. However, the absence of biochemical target validation and the predicted toxicological liabilities indicate that HTS00019 remains an early-stage hit requiring mechanistic confirmation and structural optimization. - Source: PubMed
Publication date: 2026/07/10
Al-Najjar Belal OHelal MSaqallah Fadi GBandy B - Colorectal cancer (CRC) remains a leading cause of cancer-related death, highlighting an unmet need for robust, mechanistically grounded prognostic biomarkers. Through an integrative multi-omics approach, we identified and validated a novel three-gene signature for CRC. Utilizing paired tumor and adjacent tissues from 15 patients, public datasets (TCGA, GSE231559), and machine learning (LASSO, SVM-RFE), we derived a signature comprising ABCE1, ATAD5, and FUT4. These genes were consistently upregulated in tumors, as confirmed by qPCR, and are functionally linked to core oncogenic pathways: ABCE1 (protein synthesis/immune modulation), ATAD5 (DNA replication stress response), and FUT4 (cell adhesion/immune evasion). The signature demonstrated high diagnostic accuracy (AUC 0.85) and significant prognostic value, stratifying patients into distinct risk groups with divergent survival outcomes. Single-cell RNA-seq analysis localized expression to specific cellular compartments, while immune deconvolution revealed a correlated macrophage-dominated microenvironment. A clinically interpretable nomogram was developed with excellent calibration. This study establishes a compact, biologically coherent three-gene signature as a promising tissue-based molecular classifier for CRC, offering novel insights into the intertwined mechanisms of metabolism, genomic instability, and immune suppression, and presenting potential targets for therapeutic development. - Source: PubMed
Publication date: 2026/06/18
Wang YongWang TianbingHe JianZhang TaoJin RongChen DalongHu ZhiqiPang QingLiu Huichun