SUMMARY PARAGRAPH for RAD18
RAD18 encodes an E3 ubiquitin ligase required for postreplicational DNA repair (PRR) (4 and reviewed in 5). Rad18p promotes replication through DNA lesions located at stalled replication forks through both error-prone and error-free translesion repair. It is a member of the RAD6 epistasis group of DNA repair factors which also includes Rad6p, Rad5p, Mms2p, Ubc13p, Pol30p, Rev1p, Rev3p, Rev7p, and Srs2p (reviewed in 5 and 6).
Rad18p forms a stable heterodimer with Rad6p that possesses ubiquitin conjugating, single-stranded DNA binding, and DNA-dependent ATPase activities (1). Upon DNA damage, Rad6p-Rad18p monoubiquitinates Pol30p (PCNA) at lysine residue 164 to activate translesion repair via polymerases eta (Rad30p) and zeta (Rev3p and Rev7p). Monoubiquitinated PCNA can be subsequently polyubiquitinated in a Rad5p-Mms2p-Ubc13p dependent manner to promote error-free postreplicational repair (7, reviewed in 5).
Rad18p contains both RING finger and zinc finger motifs which are thought to facilitate protein-protein interaction and DNA binding (8, 9). Transcription of RAD18 is induced up to four-fold both by UV irradiation and during meiosis. Increased RAD18 meiotic expression also coincides with peak levels of meiotic recombination (10).
rad18 null mutants are viable but highly sensitive to a broad range of DNA-damaging agents, such as UV and ionizing radiation and alkylating agents (11, 12, 13). RAD18 and its role in postreplication repair is highly conserved and similar genes have been identified in other eukaryotes such as S. pombe, mouse, and human (14, 15, 16).
Last updated: 2006-07-21