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Replication factor C subunit 3 (RFC3) is a 38 kDa protein encoded by the RFC3 gene in humans and is one of five distinct subunits (140, 40, 38, 37, and 36 kDa) of the replication factor C (RFC) complex. The RFC complex acts as a DNA clamp loader, essential for elongation of primed DNA templates by DNA polymerases delta and epsilon. Specifically, RFC3 facilitates interaction between the largest 140 kDa subunit (RFC1) and a core RFC subcomplex comprising the 36, 37, and 40 kDa subunits, and is necessary for ATP-dependent loading of proliferating cell nuclear antigen (PCNA) onto DNA—an essential step in DNA replication and repair. Mutations or altered expression of RFC3 are implicated in cancer biology and rare developmental disorders. Supporting details: - RFC3 has documented protein–protein interactions, notably with PCNA, BRD4, CHTF18, and other RFC subunits. - Its gene is referenced in multiple databases: HGNC: 9971, NCBI Gene: 5983, UniProtKB: P40938. - No direct drugs appear in clinical use that target RFC3 specifically, though it and related pathways are being explored as therapeutic and prognostic biomarkers in oncology.
Drugs targeting RFC3 would be expected to interfere with DNA replication/repair by inhibiting ATP-dependent loading of PCNA onto DNA (no approved drugs directly target RFC3 as of the latest data)
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