E3 ubiquitin-protein ligase RAD18 (RAD18)

**E3 ubiquitin-protein ligase RAD18** (RAD18) is an E3 ubiquitin ligase enzyme that plays a crucial role in the postreplication repair of damaged DNA[1][7]. It is highly conserved from yeast to humans, operating through interactions with E2 ubiquitin-conjugating enzymes such as RAD6 (UBE2A/UBE2B), particularly at sites of DNA damage[2][3]. RAD18 mediates the monoubiquitination of proliferating cell nuclear antigen (PCNA), which facilitates translesion synthesis—allowing specialized polymerases to replicate DNA past lesions[4][6]. Beyond its classical role in replication fork progression, RAD18 also participates in DNA double-strand break repair by promoting homologous recombination and recruiting the SMC5/6 complex to DNA breaks[8]. Structural domains of RAD18 include an N-terminal RING finger domain (catalytic, mediating E2 binding, and dimerization), a central zinc-finger domain (potential DNA binding, dimerization), a SAP domain (DNA binding), and a C-terminal RAD6-binding domain[3][5][6]. Mutations in RAD18 can lead to hypersensitivity to DNA-damaging agents, defective DNA repair, and have been implicated in the development of cancer due to compromised genome integrity[8]. RAD18 has no currently approved pharmacological modulators, but its central role in DNA repair makes it a potential therapeutic target and a biomarker candidate in oncology.

Other names

RNF73hHR18hRAD18Postreplication repair protein RAD18RING finger protein 73RING-type E3 ubiquitin transferase RAD18RAD18 homolog (S. cerevisiae)postreplication repair protein hRAD18p

Not applicable (no approved drugs or inhibitors directly targeting RAD18 as of current knowledge)