HUS1

更新于：2025-05-07

基本信息

别名

Checkpoint protein HUS1、hHUS1、HUS1

+ [1]

简介

Component of the 9-1-1 cell-cycle checkpoint response complex that plays a major role in DNA repair (PubMed:21659603). The 9-1-1 complex is recruited to DNA lesion upon damage by the RAD17-replication factor C (RFC) clamp loader complex (PubMed:21659603). Acts then as a sliding clamp platform on DNA for several proteins involved in long-patch base excision repair (LP-BER) (PubMed:21659603). The 9-1-1 complex stimulates DNA polymerase beta (POLB) activity by increasing its affinity for the 3'-OH end of the primer-template and stabilizes POLB to those sites where LP-BER proceeds; endonuclease FEN1 cleavage activity on substrates with double, nick, or gap flaps of distinct sequences and lengths; and DNA ligase I (LIG1) on long-patch base excision repair substrates (PubMed:21659603). The 9-1-1 complex is necessary for the recruitment of RHNO1 to sites of double-stranded breaks (DSB) occurring during the S phase (PubMed:21659603).

关联

100 项与 HUS1 相关的临床结果

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100 项与 HUS1 相关的转化医学

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0 项与 HUS1 相关的专利（医药）

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305

项与 HUS1 相关的文献（医药）

2025-06-01·Food and Chemical Toxicology

Arsenolipid-induced reproductive toxicity in Caenorhabditis elegans: Elucidating the mechanism through the HUS-1-CEP-1-EGL-1-CED-9-CED-4-CED-3 signaling pathway

Article

作者: Cheung, Kit-Leong ; Song, Bingbing ; Li, Caiyan ; Li, Rui ; Zhao, Qiaoli ; Chen, Jianping ; Wang, Zhuo ; Jia, Xuejing ; Zhong, Saiyi ; Liu, Xiaofei

Arsenolipid (AsL) is a complex lipid-soluble organic arsenic compound, which is usually found in marine organisms. Among them, arsenic-containing hydrocarbons (AsHCs) are a common type. At present, the toxic effects of different AsHCs have not been elucidated due to their different hydrocarbon chain lengths and large numbers. A model Caenorhabditis elegans (C.elegans) was used to study the reproductive toxicity and mechanism of AsHC 332, AsHC 346 and AsHC 360, which are commonly found in seafood. The results showed that three different molecular weights of AsLs reduced the number of offspring and gonadal area of C. elegans, prolonged the generation time. Meanwhile, the three AsLs regulated the expression levels of oxidative stress genes (isp-1, mev-1, sod-3, gas-1), resulting in changes in the expression of apoptosis-related genes (ced-3, ced-4, ced-9) and DNA damage-related genes (hus-1, clk-2, cep-1 and egl-1). In addition, the mechanism of arsenolipid-induced nematode reproductive toxicity was further elucidated through the HUS-1-CEP-1-EGL-1-CED-9-CED-4-CED-3 signaling pathway. Therefore, our results suggest that AsHC 332 is more exposed to reproductive toxicity than AsHC 346 and AsHC 360, which is related to changes in physicochemical properties and DNA damage-induced germ cell apoptosis.

2025-05-01·Ecotoxicology and Environmental Safety

Chlorantraniliprole-induced oxidative stress, DNA damage, and apoptosis in Caenorhabditis elegans: Mechanistic insights and ecological risk implications

Article

作者: Hu, Guokun ; Ji, Xiaoxue ; Han, Shaohua ; Qiao, Kang ; Yang, Mengzhen ; Hu, Fengyuan

Chlorantraniliprole (CAP) is one of the most widely used insecticides in the world. CAP is strictly restricted in foodstuff with maximum residual limits (MRLs) from 0.01 to 40 mg/kg set by Chinese national food safety standard. However, a detailed evaluation on its possible acute toxicity and the underlying mechanisms remains inconclusive. In this study, effects of CAP at environmentally relevant concentrations on growth, locomotion, lifespan, reproduction, and antioxidative defense systems were evaluated using the model organism Caenorhabditis elegans. Exposure to CAP notably reduced nematode development, head thrash, and pharyngeal pumping frequency compared with the control. Moreover, CAP at 0.1, 1, and 10 μg/L decreased lifespan of nematodes by 23.73 %, 28.71 %, and 36.23 %, respectively. CAP at 1 and 10 μg/L enhanced the ROS level, reduced the activity of antioxidative enzyme, including CAT and SOD. CAP also regulated mRNA expression levels of daf-16, skn-1, sod-3, gst-4, ced-3, ced-4, ced-9, egl-1, clk-2, and hus-1 in the nematodes, while no significant effect in the mutants was observed. Pearson correlation analysis revealed that significant correlation existed between tested parameters, indicating that CAP caused a series of negative effects in the nematodes. Meanwhile, molecular docking results revealed the potential of CAP to bind with oxidative stress, DNA damage and apoptosis proteins, providing molecular mechanisms for the observed detrimental effects. Therefore, our results suggested that acute exposure to CAP at environmental concentrations caused oxidative stress, DNA damage and apoptosis in the nematodes. Our results shed new light on risk assessment and management of CAP.

2025-05-01·DNA Repair

The differential roles of rad9 alternatively spliced forms in double- strand DNA break repair during Drosophila meiosis

Article

作者: Sheikh-Suliman, Suad ; Goldstein, Bareket ; Abdu, Uri ; Bakhrat, Anna

The 9-1-1 complex, comprising the Rad9, Hus1 and Rad1 proteins, is believed to operate as a component of a DNA damage checkpoint pathway. Our initial analysis of the Drosophila hus1 gene showed that Hus1 plays a dual role in meiosis, regulating both meiotic DNA damage checkpoint and homologous recombination repair. In this study, we further analyzed the meiotic roles of another protein in the complex, Rad9, which has two alternatively spliced forms, Rad9A and Rad9B. Using CRISPR/Cas9, we generated flies mutant for both rad9 isoforms. We found that, similarly to hus1, mutations in rad9 lead to female sterility. Also, double-strand DNA breaks (DSBs) that form during meiosis are not processed efficiently, and the DNA within the oocyte nucleus fails to form its characteristic shape in rad9 mutants. On the other hand, the hus1 mutation completely disrupts checkpoint activation in DSB repair enzyme mutants, whereas the rad9 mutation only partially impairs checkpoint activation in this context. Moreover, spatial rescue experiments revealed that Rad9B is efficient in repairing meiotic DSBs, while Rad9A is not. Furthermore, we found that female fertility in rad9 mutants depends on early efficient meiotic DSB repair but not on karyosome formation. In summary, our results demonstrate a differential role of Rad9 alternatively spliced forms during Drosophila meiosis in oogenesis, and while former studies showed that Hus1 is sufficient for the effective activation of the meiotic recombination checkpoint, our results revealed that this is not true for Rad9.

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