Unconventional Ubiquitin Recognition by the Ubiquitin-Binding Motif within the Y-Family DNA Polymerases ι and Rev1

• Main Authors: D'Souza, Sanjay Victor (Contributor), Walker, Graham C. (Contributor), Bomar, Martha G. (Author), Bienko, Marzena (Author), Dikic, Ivan (Author), Zhou, Pei (Author)
• Other Authors: Massachusetts Institute of Technology. Department of Biology (Contributor)
• Format: Article
• Language: English
• Published: Elsevier, 2012-11-19T17:59:36Z.
• Subjects: Article
• Online Access: Get fulltext

Translesion synthesis is an essential cell survival strategy to promote replication after DNA damage. The accumulation of Y family polymerases (pol) ι and Rev1 at the stalled replication machinery is mediated by the ubiquitin-binding motifs (UBMs) of the polymerases and enhanced by PCNA monoubiquitination. We report the solution structures of the C-terminal UBM of human pol ι and its complex with ubiquitin. Distinct from other ubiquitin-binding domains, the UBM binds to the hydrophobic surface of ubiquitin centered at L8. Accordingly, mutation of L8A, but not I44A, of ubiquitin abolishes UBM binding. Human pol ι contains two functional UBMs, both contributing to replication foci formation. In contrast, only the second UBM of Saccharomyces cerevisiae Rev1 binds to ubiquitin and is essential for Rev1-dependent cell survival and mutagenesis. Point mutations disrupting the UBM-ubiquitin interaction also impair the accumulation of pol ι in replication foci and Rev1-mediated DNA damage tolerance in vivo.
National Institute of General Medical Sciences (U.S.) (Grant GM-079376)
American Cancer Society. Research Professorship
National Institute of Environmental Health Sciences (Grant P30 ES-002109)