Ask about this productRelated genes to: FANCA antibody
- Gene:
- FANCA NIH gene
- Name:
- FA complementation group A
- Previous symbol:
- FACA, FANCH
- Synonyms:
- FAA, FA-H, FAH
- Chromosome:
- 16q24.3
- Locus Type:
- gene with protein product
- Date approved:
- 1995-12-22
- Date modifiied:
- 2019-04-23
Related products to: FANCA antibody
Related articles to: FANCA antibody
- Synthetic lethality (SL) underlies the success of PARP1 inhibitors (PARPi) in treating homologous recombination (HR)-deficient cancers, yet their broader applicability beyond HR deficiency remains poorly defined. Here, we performed an in vivo CRISPR screen that identifies FANCA deficiency as a driver of tumor progression and PARPi SL, validated across diverse human cancer models. Notably, FANCA loss does not impair HR but instead disrupts FEN1 recruitment to replication forks, leading to defective Okazaki fragment maturation, lagging-strand single-strand DNA gap accumulation, and RPA exhaustion upon PARPi treatment. Additionally, FANCA loss in oncogene-expressing cells promotes transcription-replication conflict (TRC) accumulation selectively on the lagging strand and sensitizes HR-proficient cells to PARPi, a phenotype reversible by RNA polymerase II inhibition or RNase H overexpression. Together, these findings identify FANCA deficiency as a context-specific PARPi vulnerability and establish FANCA as a key suppressor of TRCs required for genomic stability under oncogenic replication stress. - Source: PubMed
Publication date: 2026/06/16
Wang QinhongEllington Simon WGuerra PaoloGharibpoor FaezeSimpson Dennis ACho Min-GukBeltran AdrianaGupta Gaorav P - Patients with Fanconi anemia (FA) are particularly susceptible to developing squamous cell carcinoma of the head and neck due to impaired DNA repair pathways. However, their hypersensitivity to DNA damaging agents can limit effective treatment with standard radiotherapy due to severe side effects and complications. In pre-clinical models, ultra-rapid FLASH radiotherapy (FLASH) reduces radiation-induced toxicity in normal tissues while maintaining similar tumor control compared to conventional dose rate radiotherapy (CONV). Here, we investigated the safety of FLASH for treatment of the head and neck in a mouse model of FA. 129/Sv wild-type (WT) and -deficient ( ) mice received single-dose oral cavity irradiation with electron beam FLASH or CONV to evaluate radiation-induced toxicity in non-tumor-bearing mice. WT and mice were irradiated with 25 and 18 Gy, respectively, of FLASH (190 Gy/sec) or CONV (0.2 Gy/sec), with tongues harvested at 12 hours (hpi) and 10 days (dpi) post-irradiation. At 10 dpi, FLASH-irradiated tongues in both genetic backgrounds demonstrated reduced ulceration at the dorsal tongue surface compared to CONV-irradiated counterparts. Histopathological analysis of the tongue revealed lower mucositis severity scores with decreased epithelial thinning and ulceration in FLASH-irradiated tongues compared to CONV-irradiated ones. Analysis of γ-H2AX foci formation at 12 hpi demonstrated fewer foci in WT mice treated with FLASH compared to CONV, with a similar trend observed in mice. These findings suggest a potential normal tissue-sparing effect with FLASH and hold important clinical implications for the treatment of patients with Fanconi anemia and head and neck cancers. - Source: PubMed
Publication date: 2026/05/28
Loo PhoebePan MargaretZhao ManMelemenidis StavrosChen DixinWhitmore LucyRichter SaraDirbas Frederick MCasey Kerriann MGraves Edward EEpperly Michael WGreenberger JoelLoo Billy WRankin Erinn B - Fanconi anemia (FA) is a rare inherited disorder associated with impaired DNA repair, characterized by congenital anomalies, bone marrow failure, and a significantly increased risk of developing malignancies, particularly squamous cell carcinoma (SCC) of the head and neck. Treatment options for advanced SCC in FA are limited due to hypersensitivity to DNA-damaging agents. This article presents a unique case of SCC that developed in a 17-year-old patient with FA caused by a homozygous mutation in the gene. At the age of 10, he received a bone marrow transplant from a compatible related donor. Conditioning therapy included busulfan, thymoglobulin, and fludarabine, while graft-versus-host disease (GvHD) prophylaxis was administered with rituximab, methotrexate, and cyclosporine A. Nevertheless, he developed chronic cutaneous GVHD, which was treated for four years with ruxolitinib and tacrolimus, achieving only partial control. During this period, locally advanced cutaneous SCC (T3N0M0, stage III) manifested on the face. Surgery, radiation therapy, and immunotherapy with pembrolizumab led only to an initial partial response. This first pediatric case of immunotherapy for SCC in FA highlights the challenges of treating this rare patient group. Nevertheless, combining radiation therapy with immunotherapy may represent a possible option for disease control. - Source: PubMed
Publication date: 2026/05/14
Zelenova EkaterinaBelysheva TatianaOrlova KristinaGrigorenko VasilySemenova VeraSharapova ElenaVishnevskaya YanaSamoylenko IgorNasedkina TatianaValiev TimurPolyakov VladimirVarfolomeeva Svetlana - Host genetic variability, particularly involving inborn errors of immunity (IEI), has emerged as a critical determinant of interindividual differences in COVID-19 severity, yet comprehensive genomic characterization of IEI-related variants in admixed Latin American populations remains scarce. - Source: PubMed
Publication date: 2026/05/26
Barros de Oliveira Sá Marcus VillanderRocha Gabriela DiasSilveira Oliveira Pablo RafaelCampos Túlio de LimaLisbôa Furtado Guilherme TorresGaldino Galisa Steffany LarissaSilva Andreia SoaresMoura PatriciaSão Pedro Raquel Bispo deTavares Natália MachadoBoaventura Viviane SampaioNunes SaraBonyek-Silva IcaroCaldas Juliana RibeiroRoma Eric HenriqueAlmeida Jorge ReisSilva Andrea AliceBaccin TatianaCastro Andrea Cauduro deRosario Vallinoto Antônio Carlosda Silva RosileneMelo Dos Santos Eduardo JoséGarcia Cristiana CoutoSlhessarenko Renata DezengriniArmstrong Anderson da CostaCarmo Rodrigo FelicianoSilva Vasconcelos Luydson Richardson - Interstrand crosslinks are cytotoxic lesions that inhibit essential processes including replication and transcription. Replication fork reversal occurs in response to interstrand crosslink inducing drug, MMC, but how replication fork reversal promotes repair of interstrand crosslinks is poorly understood. Here, we investigated the role of the RAD54L translocase in interstrand crosslink repair. We found RAD54L is required to promote nascent DNA degradation in FANCD2 and FANCA-depleted cells consistent with a previous study indicating RAD54L promotes replication fork reversal. We further show RAD54L activity is required for formation of radial chromosomes in FANCD2-deficient cells suggesting fork reversal may be required to generate the intermediate undergoing aberrant fusion in FANC-deficient cells. Finally, we demonstrate FANCD2 foci accumulate and DSBs persist in RAD54L-deficient cells indicating RAD54L is required for efficient repair of DSBs. Together, our results indicate RAD54L plays multiple roles in efficient processing and repair of interstrand crosslinks. - Source: PubMed
Publication date: 2026/05/15
Tolbert ZaneReed SamanthaGoodson StevenMason Jennifer M