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The Oligomeric State of Rad6-Rad18 and Its Interactions with Translesion Synthesis Proteins
Journal article   Open access   Peer reviewed

The Oligomeric State of Rad6-Rad18 and Its Interactions with Translesion Synthesis Proteins

Tyler J. Woodward, Brittany M. Ripley, Justin A. Ling and M. Todd Washington
Biomolecules (Basel, Switzerland), Vol.16(8), 1172
08/12/2026
DOI: 10.3390/biom16081172
PMCID: PMC13510358
PMID: 42650838
url
https://doi.org/10.3390/biom16081172View
Published (Version of record) Open Access

Abstract

Translesion synthesis is a major DNA damage bypass pathway in which specialized DNA polymerases, such as pol η and Rev1, are recruited to stalled replication forks where they catalyze nucleotide incorporation opposite DNA damage. Translesion synthesis is regulated by the Rad6-Rad18 complex, which catalyzes PCNA mono-ubiquitylation. Despite its central role in regulating translesion synthesis, its oligomeric state and molecular interactions are poorly understood. Here, we use mass photometry to show that Rad18 co-purifies with Rad6 and forms a series of larger oligomeric complexes. Using yeast two-hybrid studies, we showed that while the full-length Rad18 complex interacts with pol η, its interaction with Rev1 is controlled by auto-inhibition. The release of this auto-inhibition is associated with the dissociation of the Rad6-Rad18 complex, freeing Rad18 monomers and dimers. Because pol η participates in non-mutagenic translesion synthesis, while Rev1 participates in mutagenic translesion synthesis, this auto-inhibition likely allows pol η preferential access to stalled replication forks by delaying Rev1 recruitment. Such an ordered polymerase-recruitment mechanism would reduce the likelihood of mutations.
 DNA replication DNA damage DNA repair mutagenesis

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