Ask about this productRelated genes to: RAD51AP1 antibody
- Gene:
- RAD51AP1 NIH gene
- Name:
- RAD51 associated protein 1
- Previous symbol:
- -
- Synonyms:
- PIR51
- Chromosome:
- 12p13.32
- Locus Type:
- gene with protein product
- Date approved:
- 2004-09-16
- Date modifiied:
- 2016-10-05
Related products to: RAD51AP1 antibody
Related articles to: RAD51AP1 antibody
- Glioblastoma multiforme (GBM) is the most prevalent primary brain tumor in adults and characterized by high therapeutic resistance and poor prognosis, in which the repair of DNA damage plays a significant role, highlighting the need to elucidate the regulatory mechanisms of DNA damage repair in GBM cells. The discs large homolog associated protein 5 (DLGAP5) is highly expressed and plays pro-tumoral activities in various cancers, however its roles in GBM remain poorly defined. Here, we report that DLGAP5 is significantly upregulated and associated with poor prognosis of GBM patients. In addition, DLGAP5 knockdown suppresses proliferation, induces apoptosis and causes DNA damage in GBM cells. Mechanistically, DLGAP5 knockdown leads to a decrease of E2F1-mediated transcription of DNA repair protein RAD51AP1, and importantly, the enforced expression of E2F1 recovers RAD51AP1 expression that largely rescues DNA damage and apoptosis of GBM cells depleted of DLGAP5. Furthermore, DLGAP5 knockdown reduces the expression of E2F1 and RAD51AP1 and induces DNA damage and suppresses tumorigenesis in xenografted GBM tumors. In conclusion, this study demonstrates that DLGAP5 protects against DNA damage in GBM cells through the E2F1/RAD51AP1 pathway, providing potential therapeutic targets in DNA damage-inducing anti-GBM modalities. - Source: PubMed
Publication date: 2026/04/17
Liu YujieChen RongLiu GexiChen JieZhou JingjieChen YanLi ZhiluLi YunyangDeng LongfeiCui Hongjuan - The telomere long noncoding RNA TERRA forms R-loops in vitro at telomeres in a RAD51AP1-dependent manner. In classic DNA double-strand break repair, RAD51AP1 promotes R-loop formation and enables RAD51 to form D-loops by promoting the invasion of local RNA transcripts into donor DNA to form DNA-RNA (DR)-loops. We have previously shown that cells lacking the basic domain of TRF2 and functional RAP1 accumulate telomere D-loops, resulting in homology-directed repair (HDR)-mediated telomere-telomere clustering and formation of ultrabright telomeres (UTs). TRF2B also cooperates with RAP1 to repress telomere R-loop formation in UTs. TERRA has been shown to promote telomere HDR, associating telomeres during R-loop formation. However, the mechanism behind TERRA-mediated telomere HDR and how the TRF2-RAP1 complex regulates telomere R-loops remain unclear. Using reconstituted biochemical systems, we found that RAD51AP1 and TERRA-dependent R-loops promote RAD51-mediated telomere D-loop formation in a TERRA length- and sequence-dependent manner. Specifically, RAD51-ssDNA filaments capture telomere R-loops preferentially over dsDNA. We also discovered that BLM's interaction with the TRF2-RAP1 complex is required to promote BLM helicase-mediated unwinding of telomere R-loops. Importantly, BLM-deficient cells and cells reconstituted with BLM mutants unable to interact with TRF2 accumulate telomere R-loops in UTs. Our findings highlight a novel mechanism revealing that the TRF2-RAP1-BLM complex removes R-loops at telomeres to inhibit the generation of telomere D-loops, thus repressing telomere HDR and UT formation. - Source: PubMed
Liang FengshanChang Sandy - Glutamine is an essential amino acid for tumor survival, but therapies targeting glutamine metabolism have largely failed due to adaptive resistance mechanisms. Here, we identify the pseudokinase TRIB3 as a key mediator of the metabolic adaptation of hepatocellular carcinoma (HCC) cells to limiting glutamine availability. TRIB3 is upregulated under glutamine deprivation in a c-Jun-dependent manner, functioning in the nucleus to safeguard DNA repair fidelity, allowing the timely resolution of DNA damage and preventing replication catastrophe. TRIB3 binds to G-quadruplex DNA (G4-DNA) structures throughout the genome, recruiting the helicase DDX5 to resolve them as a cooperative functional complex. Depleting TRIB3 or DDX5 in HCC cells leads to exaggerated G4-DNA accumulation and heightened DNA damage associated with the downregulation of DNA damage repair (DDR) pathways. We illustrate this effect on homologous recombination (HR) pathway genes, finding that TRIB3-DDX5 prevents G4-DNA accumulation at the BRCA1 and RAD51AP1 promoter regions that would otherwise suppress transcription. In vivo, TRIB3 silencing suppresses HCC xenograft growth, patently increasing DNA damage and apoptosis when mice were maintained on glutamine-deficient diets. Clinically, TRIB3 is overexpressed in HCC and correlates with poor prognosis. Our results propose the TRIB3-DDX5-G4 axis as a therapeutic target in HCC and other TRIB3-high malignancies. - Source: PubMed
Publication date: 2026/03/07
Ji QiangSun XuedanSun ZhangranLi MengfanCheng XinyuTian ShuaiThorne Rick FLi JinmingLiu GuangzhiWu MianLiu Xiaoying - Ovarian cancer, the eighth leading cause of cancer-related deaths globally, is projected to result in approximately 307,000 deaths by 2040. So, identifying novel therapeutic compounds is critical to improving the survival rate of patients with ovarian cancer. Calycosin, derived from Astragalus root, has demonstrated anti-cancer properties, suggesting its possible use for treating ovarian cancer. In the present study, we synthesized and evaluated a series of calycosin derivatives (H1-H10) to enhance its therapeutic efficacy against ovarian cancer. Among these, calycosin derivative H10 exhibited the most potent anti-cancer activity, effectively inhibiting cell proliferation, migration, and colony formation abilities in SKOV3 and A2780 ovarian cancer cell lines. In addition, H10 induced G0/G1 cell cycle arrest and dose-dependent apoptosis in these cells. Further, comparative proteomic analysis coupled with Ingenuity Pathway Analysis was used to delineate the molecular mechanisms underlying the anti-ovarian cancer effect. Our results demonstrated that H10 modulated key biological processes related to DNA damage response, chromatin and kinase activities, ferroptosis, FoxO signaling, and p53 signaling in ovarian carcinoma. Specifically, H10 regulated a protein cluster comprising RAD51AP1, USP1, USP22, DDX11, ACSL4, GPX4, NCOA4, CCNB1, and CDK1, which are critical to ovarian tumorigenicity. Functional assays confirmed H10's ability to induce cell cycle arrest, senescence, and apoptosis, while proteomic analysis further highlighted its regulatory role in cell cycle regulation and ferroptosis. These findings identify calycosin H10 as a promising therapeutic candidate for ovarian cancer, offering novel insights into its molecular mechanisms of action. - Source: PubMed
Publication date: 2026/01/14
Yang FuhongLi XinGao HanchiYao PeiQin XianLin XiaoLai Keng PoTian JingChen Jian - Homology-directed DNA repair (HDR) is critical for genome stability and tumor suppression. HDR is initiated by the RAD51 single-stranded (ss)DNA nucleoprotein filament, which conducts the homology search and invades a homologous DNA template, creating a displacement-loop (D-loop). The RAD51 filament is assisted in these processes by several proteins. One such protein is RAD51-associated protein 1 (RAD51AP1), which binds DNA and RNA and directly interacts with RAD51. Of note, RAD51AP1 overexpression is associated with poor prognosis in several different cancer types. Here, we show that RAD51AP1 activity is regulated by phosphorylation. RAD51AP1 bearing S277/282A mutations is more proficient in the stimulation of D-loop formation than wild-type RAD51AP1 or phosphomimetic RAD51AP1-S277/282D. In EMSAs, RAD51AP1 with S277/282A mutations more avidly binds ssDNA, double-stranded (ds)DNA, and the nucleosome core particle than wild-type RAD51AP1 or RAD51AP1-S277/282D. In cells, RAD51AP1-S277/282A confers no rescue of RAD51AP1 deficiency in toxicity tests and DNA replication assays. In contrast, RAD51AP1-S277/282D fully rescues RAD51AP1 deficiency. We provide evidence that RAD51AP1-S277 is a CDK2 target and propose a model in which RAD51AP1-S277/282 phosphorylation ensures RAD51AP1 flexibility for dynamic engagement in consecutive steps of the HDR reaction. Our results provide new mechanistic insights into RAD51AP1 regulation by a CDK. - Source: PubMed
Publication date: 2026/01/12
Sharma NeelamUhrig Mollie EKwon YounghoSung PatrickWiese Claudia