1 research outputs found
Chemical Protein Polyubiquitination Reveals the Role of a Noncanonical Polyubiquitin Chain in DNA Damage Tolerance
Polyubiquitination of proteins regulates
a variety of cellular
processes, including protein degradation, NF-κB pathway activation,
apoptosis, and DNA damage tolerance. Methods for generating polyubiquitinated
protein with defined ubiquitin chain linkage and length are needed
for an in-depth molecular understanding of protein polyubiquitination.
However, enzymatic protein polyubiquitination usually generates polyubiquitinated
proteins with mixed chain lengths in a low yield. We report herein
a new chemical approach for protein polyubiquitination with a defined
ubiquitin chain length and linkage under a mild condition that preserves
the native fold of the target protein. In DNA damage tolerance, K63-polyubiquitinated
proliferating cell nuclear antigen (PCNA) plays an important yet unclear
role in regulating the selection of the error-free over error-prone
lesion bypass pathways. Using the chemically polyubiquitinated PCNA,
we revealed a mechanism of the K63 polyubiquitin chain on PCNA in
promoting the error-free lesion bypass by suppressing the DNA translesion
synthesis (TLS)