Ask about this productRelated genes to: RAD9A Blocking Peptide
- 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 Blocking Peptide
Related articles to: RAD9A Blocking Peptide
- Triple negative breast cancer (TNBC) and ovarian cancer share many molecular features and are primarily treated with surgical resection and aggressive chemotherapy regimens. Unfortunately, survival rates for patients with advanced metastatic disease are poor, highlighting the need for innovative therapeutic approaches. - Source: PubMed
Publication date: 2026/07/20
Wang XiyinEmch Michael JVoll Lauren AEpp RebeccaRodman Esther P BOdell Noa JSmith Hannah MPearson Nicole AHou XiaonanLi YaLarson Melissa COberg Ann LHitosugi TaroGoetz Matthew PKaufmann Scott HWeroha S JohnBeer Philip AHawse John R - Mutations in the ATRX chromatin remodeler confer a predisposition to a developmental genetic disorder and cancer, but how ATRX safeguards genome and telomere stability remains unresolved. Here, we uncover critical dependencies for the CTC1-STN1-TEN1 (CST) complex and RAD9A-HUS1-RAD1 (9-1-1) clamp in ATRX-deficient cells. ATRX-CST synthetic lethality manifests following accumulation of telomeric G-rich single-stranded DNA (ssDNA), which results in telomere loss and cell death. Conversely, we attribute ATRX-9-1-1 synthetic lethality to genome-wide ssDNA lesions, which compromise DNA replication. We further show that ATRX suppresses DNA damage during replication stress by counteracting the activity of the FAM111A protease. We demonstrate that roles of ATRX in telomere maintenance and replication are genetically separable, requiring its ATPase activity and PIP-box, respectively. We also show that such roles protecting genome stability are largely independent of the ATRX-DAXX interaction. Collectively, our data show that functions of ATRX in suppressing toxic ssDNA lesions are context-dependent and are key to global DNA replication and telomere integrity. - Source: PubMed
Publication date: 2026/06/30
Segura-Bayona SandraMaric MarijaTakaki TohruManova ZornitsaStanage Tyler HIdilli Aurora ILi ShudongHewitt GraemeMachour Feras EMillar RhonaAdamowicz MarekLow Ronnie Ren JieRuis PhilAzeroglu BenuraFallesen ToddPatel HarshilHowell StevenKotsantis PanagiotisHowell MichaelBoulton Simon J - Tousled-like kinases 1 and 2 (TLK1 and TLK2) are paralogous serine/threonine kinases that share high sequence similarity yet exhibit functional divergence in cellular processes such as DNA replication, damage response, and chromatin organization. This study elucidates the paralog-specific co-phosphoregulatory networks underlying this divergence through a comprehensive analysis of 3825 human phosphoproteomic articles. Predominant phosphosites were identified as S134 and T38 for TLK1 and S73, S99, and S111 for TLK2, revealing context-dependent regulation across cancers and perturbations. Co-phosphoregulation analyses uncovered distinct networks: TLK1 associates with DNA damage signaling via proteins like ABRAXAS1, PML, and RAD9A, while TLK2 integrates with chromatin remodeling and replication through CHD4, DOT1L, NASP, and RNF20. Upstream kinases for TLK2, predominantly CDKs, link it to cell-cycle progression, whereas downstream substrates and binary interactors converge on genome stability pathways with paralog-specific nuances. These findings highlight the potential role of TLK1 on checkpoint activation and TLK2 on replication-coupled chromatin maintenance, providing insights into their roles in cancer amplification and therapeutic resistance, as well as neurodevelopmental disorders, where emerging evidence also support the involvement of TLK1 alongside TLK2. - Source: PubMed
Publication date: 2026/06/20
Vijayan JishnaSubair SuhailAhmed MukhtarGopalakrishnan Athira PerunellySambreena AlimathJohn LevinRaju RajeshRajeev Athira C - Cancer cells, like yeast, use fermentation despite the presence of oxygen, a phenomenon called aerobic glycolysis. The advantage is that it maintains many C-C bonds of glucose, allowing highly proliferating cells to produce the biomolecules that are necessary for cytokinesis. However, aerobic glycolysis is less energy-efficient than respiration, and it must operate at high frequency and produces large amounts of lactate, which modifies and stimulates DNA repair enzymes via lysine lactylation. This makes cancer cells resistant to radiotherapy, which requires a combination with chemotherapy using drugs that inhibit DNA repair. However, this converts healthy cells to cancer cells, indicating that research is still required regarding the relationship between glycolysis and cancer. Using yeast as a model, we discovered that the glycolytic enzymes TPI and GAPDH (Tpi1p and Tdh1-3p in yeast) interact with the DNA damage-dependent Checkpoint Rad9p (53BP1/BRCA1/MDC1 in humans). We propose that Tpi1p and Tdh1-3p override Rad9p, allowing cells with damaged DNA to proliferate. We isolated and mutant strains that are deficient in DNA repair. While the mutant strain has lower enzymatic activity, the mutant strains have normal enzymatic activity, confirming previous reports that GAPDH moonlights in the DNA damage response. - Source: PubMed
Publication date: 2026/06/12
Chua Vivienne X YYip Joyce M XCho Melody T KLin Sumi Z QTan RichLee Donna G KDai KexinLim Teck KLin QingsongLehming-Teo RachelPines OphryLehming Norbert - 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