E3 ubiquitin-protein ligase RAD18 is an
enzyme
An enzyme () is a protein that acts as a biological catalyst by accelerating chemical reactions. The molecules upon which enzymes may act are called substrate (chemistry), substrates, and the enzyme converts the substrates into different mol ...
that in humans is encoded by the ''RAD18''
gene
In biology, the word gene has two meanings. The Mendelian gene is a basic unit of heredity. The molecular gene is a sequence of nucleotides in DNA that is transcribed to produce a functional RNA. There are two types of molecular genes: protei ...
.
A knockout in a human colorectal cancer cell line, HCT116, has also been created.
Function
The protein encoded by this gene is highly similar to
S. cerevisiae DNA damage repair protein Rad18. Yeast Rad18 functions through interaction with Rad6, which is a ubiquitin-conjugating enzyme required for post-replication repair of damaged DNA. Similar to its yeast counterpart, this protein is able to interact with the human homolog of yeast Rad6 protein through a conserved
ring finger motif. Mutation of this motif results in defective replication of UV-damaged DNA and hypersensitivity to multiple mutagens.
RAD18 is an E3
ubiquitin ligase
A ubiquitin ligase (also called an E3 ubiquitin ligase) is a protein that recruits an E2 ubiquitin-conjugating enzyme that has been loaded with ubiquitin, recognizes a protein substrate, and assists or directly catalyzes the transfer of ubiquitin ...
that enables movement of
ubiquitin
Ubiquitin is a small (8.6 kDa) regulatory protein found in most tissues of eukaryotic organisms, i.e., it is found ''ubiquitously''. It was discovered in 1975 by Gideon Goldstein and further characterized throughout the late 1970s and 19 ...
from a ubiquitin carrier to another protein (the substrate). One activity of RAD18 is to prevent
replication fork collapse by promoting DNA translesion synthesis and template switching.
RAD18 is also involved in directing repair of DNA double-strand breaks by
homologous recombination
Homologous recombination is a type of genetic recombination in which genetic information is exchanged between two similar or identical molecules of double-stranded or single-stranded nucleic acids (usually DNA as in Cell (biology), cellular organi ...
in post replicative
chromatin
Chromatin is a complex of DNA and protein found in eukaryote, eukaryotic cells. The primary function is to package long DNA molecules into more compact, denser structures. This prevents the strands from becoming tangled and also plays important r ...
.
[ RAD18 appears to promote homologous recombinational repair by recruiting the SMC5, SMC6 (SMC5/6) complex to the DNA breaks.][
]
Interactions
RAD18 has been shown to interact with HLTF,
References
Further reading
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{{refend
Genes mutated in mice
DNA repair