Ask about this productRelated genes to: RAD9B Blocking Peptide
- Gene:
- RAD9B NIH gene
- Name:
- RAD9 checkpoint clamp component B
- Previous symbol:
- -
- Synonyms:
- FLJ40346
- Chromosome:
- 12q24.11
- Locus Type:
- gene with protein product
- Date approved:
- 2003-07-21
- Date modifiied:
- 2016-10-05
Related products to: RAD9B Blocking Peptide
Related articles to: RAD9B Blocking Peptide
- 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. - Source: PubMed
Publication date: 2025/04/08
Goldstein BareketSheikh-Suliman SuadBakhrat AnnaAbdu Uri - To study telomere maintenance mechanism (TMM) activation during malignant transformation, we compared neurofibroma (NF) and malignant peripheral nerve sheath tumor (MPNST) in the same patient with type-1 neurofibromatosis (NF1), a total of 20 NF-MPNST pairs in 20 NF1 patients. These comparisons minimized genetic bias and contrasted only changes associated with malignant transformation, while subtracting changes that developed upon the transformation of normal cells to the benign tumor. TGF-β superfamily genes were found to activate the PAX and SOX transcription factors, leading to TMM activation. BMPER activates PAX6 through BMP2 and PAX7 through BMP4; BMP15 activates SOX14; and INHBC activates PAX9 and SOX14. The activated PAX and SOX genes sequentially establish the core architecture of the RAD52-dependent alternative lengthening of telomeres (ALT). Specifically, PAX7 activates the recombinase (RAD52) and a negative regulator (SLX4IP). PAX6 and SOX14 activate positive regulators (BLM and BRCA2, respectively). PAX9 and SOX14 activate RAD9B and FEN1, which are responsible for the stability of homologous recombination intermediates and increase, together with RAD52, the telomere length. Telomere elongation achieved by the activation of PAX7 and PAX9 is associated with a poor prognosis. We demonstrated that TGF-β superfamily-induced transcriptional activation pathways activated the RAD52-dependent ALT during malignant transformation of MPNSTs. - Source: PubMed
Publication date: 2024/11/02
Choi EunjiLee JungwooKim HyoJuKim Young-JoonKim Seung Hyun - Oesophageal squamous cell carcinoma (ESCC) contributes to high mortality. Modulating ferroptosis may reverse resistance to radiotherapy. This article was to explore the ubiquitination modification of KLF5 and its effect on ferroptosis in ESCC. KLF5 was under-expressed by shRNA plasmids in the cells and ROS levels were analysed by flow cytometry, ferroptotic gene expression was detected by qRT-PCR, MDA and GSH levels were determined by ELISA, cell morphology was observed by transmission electron microscopy, and Fe ion levels were analysed by immunofluorescence. Cells were treated with Ferrostatin-1 and NAC and analysed for cell proliferation by colony formation assay, cell migration and invasion by Transwell assays, and apoptosis by flow cytometry. DNA damage in cells was also analysed using comet assay, EdU doping assay, γH2AX fluorescence, DNA-PKcs and PCR. NEDD4L and KLF5 binding was analysed by immunoprecipitation. Changes in ferroptosis, DNA damage and resistance were analysed in cells with both silencing NEDD4L and KLF5. Changes in tumour resistance to radiation were analysed in mice underexpressing NEDD4L and KLF5. Low expression of KLF5 significantly promotes cellular lipid peroxidation levels, with decreased expression of SOD and GPX4, and increased expression of ACSL4. Concurrently, MDA levels deplete GSH, and cells exhibit typical ferroptotic morphology with increased Fe2+ content. KLF5 inhibition results in enhanced cellular clonogenicity, migration and invasion activities, reduced apoptosis, increased tail DNA, nuclear EdU incorporation, nuclear γH2AX foci and elevated expression of DNA-PKcs, LIG4, RAD9B and BMI1. Ferrostatin-1 and NAC reverse these effects. NEDD4L ubiquitination modifies and degrades KLF5, with NEDD4L/KLF5 inhibition mitigating cellular ferroptosis and DNA damage, thereby promoting radiosensitivity both in vitro and in vivo. NEDD4L increases radiosensitivity by accelerating cellular ferroptosis via ubiquitination modification of KLF5. - Source: PubMed
Chen JinjinYing KaijunSun JianWang YaoJi MingmingSun Yunhao - Parkinson's disease (PD) is a neurodegenerative disorder that affects primarily the dopaminergic (DAergic) neurons of the mesostriatal system, among other nuclei of the brain. Although it is considered an idiopathic disease, oxidative stress is believed to be involved in DAergic neuron death and therefore plays an important role in the onset and development of the disease. RAD9B is a paralog of the RAD9 checkpoint, sharing some similar functions related to DNA damage resistance and apoptosis, as well as the ability to form 9-1-1 heterotrimers with RAD1 and HUS1. - Source: PubMed
Publication date: 2023/07/17
Barroso-Chinea PedroSalas-Hernández JosmarCruz-Muros IgnacioLópez-Fernández JonathanFreire RaimundoAfonso-Oramas Domingo - DNA damage response mechanisms have meiotic roles that ensure successful gamete formation. While completion of meiotic double-strand break (DSB) repair requires the canonical RAD9A-RAD1-HUS1 (9A-1-1) complex, mammalian meiocytes also express RAD9A and HUS1 paralogs, RAD9B and HUS1B, predicted to form alternative 9-1-1 complexes. The RAD1 subunit is shared by all predicted 9-1-1 complexes and localizes to meiotic chromosomes even in the absence of HUS1 and RAD9A. Here, we report that testis-specific disruption of RAD1 in mice resulted in impaired DSB repair, germ cell depletion, and infertility. Unlike or disruption, loss in meiocytes also caused severe defects in homolog synapsis, impaired phosphorylation of ATR targets such as H2AX, CHK1, and HORMAD2, and compromised meiotic sex chromosome inactivation. Together, these results establish critical roles for both canonical and alternative 9-1-1 complexes in meiotic ATR activation and successful prophase I completion. - Source: PubMed
Publication date: 2022/02/08
Pereira CatalinaArroyo-Martinez Gerardo AGuo Matthew ZDowney Michael SKelly Emma RGrive Kathryn JMahadevaiah Shantha KSims Jennie RFaca Vitor MTsai CharltonSchiltz Carl JWit NiekJacobs HeinzClark Nathan LFreire RaimundoTurner JamesLyndaker Amy MBrieno-Enriquez Miguel ACohen Paula ESmolka Marcus BWeiss Robert S