Ask about this productRelated genes to: RAD9A antibody
- Gene:
- RAD9A NIH gene
- Name:
- RAD9 checkpoint clamp component A
- Previous symbol:
- RAD9
- Synonyms:
- -
- Chromosome:
- 11q13.2
- Locus Type:
- gene with protein product
- Date approved:
- 1997-02-03
- Date modifiied:
- 2016-10-05
Related products to: RAD9A antibody
Related articles to: RAD9A antibody
- Replication stress is a major driver of genomic instability and contributes to diseases such as cancer. It triggers the S-phase checkpoint, a signaling pathway that coordinates the handling of replication obstacles with cell cycle progression. One prominent source of replication stress is the formation of DNA-protein crosslinks on the template, such as those induced by DNA topoisomerase I poisoning by camptothecin (CPT). Here, we investigated how the S-phase checkpoint responds to CPT-induced replication stress. We show that both activation and timely deactivation of checkpoint signaling are critical for DNA replication completion and cell viability. Using a locus-specific approach, we found that checkpoint signaling is actively dampened at lesion sites. Mechanistically, this attenuation involves the displacement of the checkpoint mediator Rad9 by the DNA repair factors Slx4 and Fun30. This local dampening not only promotes cell cycle progression, but also permits Exo1-dependent resection of replication forks stalled by Top1-DNA crosslinks. Controlled resection, in turn, allows homologous recombination factors to access and stabilize the forks, preventing their degradation. We propose that local checkpoint dampening by Slx4 and Fun30 at replication stress sites is a critical mechanism that promotes replication completion and preserves genome stability. - Source: PubMed
Courtes MathildeBoissière ThierryBarthe AntoinePasero PhilippePardo Benjamin - To maintain the integrity of the genome, cells have evolved a complex signalling system, termed the DNA damage response (DDR), which detects DNA damage and promotes DNA repair. To date, over 600 proteins have been identified that play an integral role in the DDR. RAD9, encoding a DDR mediator protein, was the prototypical DNA damage checkpoint gene, establishing the genetic regulation of transient cell-cycle delays upon DNA damage. Rad9, identified 38 years ago in the budding yeast Saccharomyces cerevisiae as a damage-dependent cell-cycle regulator, is now known to regulate additional responses to DNA damage including both cell-cycle recovery and repair. The Rad9 protein is extensively phosphorylated both during a normal cell cycle and following DNA damage and several of these modifications have been linked to specific Rad9 roles within the DDR. Proteins structurally and functionally related to Rad9 exist in mammalian cells (e.g., 53BP1, BRCA1, MDC1) and insights into their regulation and mechanism of action have been informed by studies in yeast. This review will discuss the cellular mechanisms governing the DDR with an emphasis on the multifaceted role of Rad9 in sensing and responding to DNA damage, and how phosphorylation events regulate its function within the DDR. As the cellular events governing the DDR are well conserved, discoveries in yeast can be extrapolated to humans and may lead to the identification of additional novel protein targets, with several DDR inhibitors currently in clinical use or showing promise in clinical trials. - Source: PubMed
Publication date: 2026/03/04
Kiely AO'Halloran FYoung PLowndes N FGrenon MFinn K - Activation of the ATR-dependent DNA damage response (ATR-DDR) is well characterized; however, the molecular mechanisms underlying its maintenance and inactivation remain largely elusive. Rhino is the least understood component of ATR-DDR. Structural modeling and binding free energy calculations revealed structural remodeling involving Rad17, Rad9-Hus1-Rad1 (9-1-1), and Rhino during ATR-DDR progression. Biochemical and computational analyses revealed the competitive binding of Rad17 and Rhino to the 9-1-1 complex, suggesting a structural transition from the Rad17-9-1-1 complex to the Rhino-9-1-1 complex. The presence of two conserved KYxxL+ motifs in Rhino suggests that it bridges the two 9-1-1 complexes. This enables the polymerization of multiple 9-1-1 complexes through Rhino and explains the long-standing discrepancy between the conventional model and experimental observations of Rad17 and Rad9 foci. Furthermore, structural analysis of the Rad9 C-terminal tail revealed its ability to compete with both Rhino and Rad17, leading to disassembly of the checkpoint complex and providing a mechanism for checkpoint inactivation. Quantum chemical calculations revealed comparable binding free energies for intermediate complexes. These observations suggest that the Rad17-9-1-1-Rhino complex undergoes energetically equivalent structural transitions, providing a mechanistic basis for the sequential progression of ATR-DDR. - Source: PubMed
Fukumoto YasunoriYuki RyuzaburoOgra Yasumitsu - Parasitic castration is a widespread strategy where parasites hijack host reproductive resources, yet the key molecular mechanisms driving this phenomenon remain poorly understood. Here, we reported that parasitization by the parasitic wasp triggers apoptosis-mediated castration in the larval testes of its lepidopteran host, . Such a phenomenon was mediated by , a testis-enriched (PTP) encoded by Cotesia vestalis bracovirus (CvBV), a domesticated virus endogenized in the wasp. Similarly, a homolog of CvBV_22-9, encoded by the Microplitis manilae bracovirus, is involved in testis castration by inducing apoptosis in parasitized fall armyworm, . Mechanistically, CvBV_22-9 binds to a cell cycle checkpoint protein, Rad9A, but does not alter its tyrosine phosphorylation level. Crucially, CRISPR-Cas9 knockout of causes embryonic lethality and severe testis defects. Validation in shows that testis-specific expression of or knockdown induces apoptosis, while combined targeting synergistically enhances this effect, suggesting a conserved function of both proteins in insects. Our study uncovers a regulatory mechanism where a parasitoid wasp deploys a domesticated viral PTP that functions as a pseudophosphatase to induce Rad9A-mediated apoptosis and disrupt host testis development and spermatogenesis. This mechanism highlights a sophisticated strategy of host exploitation by parasitoid wasps, providing insights for the biocontrol of lepidopteran pests. - Source: PubMed
Publication date: 2026/02/09
Gao HongshuaiGuo MujuanYang XinHu RongminWu KunPang LanYe XiqianHuang JianhuaChen XuexinWang Zhizhi - The ATR/CHK1 pathway governs a crucial intra-S-phase checkpoint that safeguards genome stability under replication stress by stabilizing stalled replication forks and ensuring high-fidelity DNA replication. Traditionally, activation of this pathway is thought to rely on replication protein A (RPA)-coated single-stranded DNA, which recruits the ATR-ATRIP complex to sites of stalling fork, positioning RPA as essential for ATR signaling. In this study, we report a surprising and previously unrecognized phenomenon: acute depletion of RPA2 triggers robust ATR/CHK1 activation through an RPA-independent mechanism. Using 293A and RPE-1 cells engineered with an inducible RPA2-dTAG degron system, we observed increased phosphorylation of CHK1 at Ser296 and Ser345 in the absence of RPA. Notably, this elevated CHK1 phosphorylation was abolished by ATR inhibition, confirming its dependence on ATR kinase activity. Mechanistic analyses further revealed that this RPA-independent activation requires the checkpoint mediators RAD9 and TOPBP1. These findings uncover dual mechanisms, both RPA-dependent and -independent, of ATR/CHK1 pathway activation, highlighting a robust and flexible replication stress response network that preserves genome integrity even when canonical signaling is disrupted. - Source: PubMed
Publication date: 2026/02/02
Huang MinZhu DandanChen Junjie