The CCDC117 Knockout 786-O Polyclonal Cells represent a CRISPR/Cas9-edited polyclonal knockout cell population derived from the 786-O human renal cell carcinoma line, designed to disrupt the CCDC117 gene. This loss-of-function model enables investigation of CCDC117 function in DNA interstrand crosslink repair and genomic stability.
The 786-O host cell line is an epithelial cell model established from a clear cell adenocarcinoma of the kidney. It harbors a VHL mutation, commonly used in kidney cancer research, and provides a relevant context for studying DNA damage response pathways in renal cell carcinoma.
CCDC117 encodes a subunit of the Fanconi anemia core complex, essential for DNA interstrand crosslink repair. It is regulated by DNA damage-activated kinases ATM and ATR and transcription factors such as E2F1. Upon activation, CCDC117 interacts with multiple core complex components, including FANCA, FANCB, FANCC, FANCE, FANCF, FANCG, FANCL, FANCM, FAAP20, and FAAP100, to promote monoubiquitination of FANCD2 and FANCI. This critical event facilitates downstream homologous recombination repair mediated by BRCA1, BRCA2, and RAD51. Disruption of CCDC117 impairs this pathway, leading to genomic instability and hypersensitivity to DNA crosslinking agents.
In the 786-O background, CCDC117 knockout provides a powerful tool to dissect the interplay between renal cell carcinoma biology and DNA repair deficiency. The VHL-mutant status of 786-O cells may further exacerbate genomic instability upon loss of CCDC117, creating a model for studying synthetic lethality and identifying potential therapeutic vulnerabilities in kidney cancer.
Applications include mechanistic studies of the Fanconi anemia pathway, DNA repair dynamics in renal cell carcinoma, screening for sensitivity to crosslinking agents such as mitomycin C, and validation of cancer therapeutic targets. Representative assays encompass Western blotting for FANCD2 monoubiquitination, mitomycin C sensitivity assays, clonogenic survival following DNA damage, immunofluorescence detection of FANCD2 foci, RNA-seq for transcriptional profiling, and cell cycle analysis. For further information, please contact Ascent Research.
