title: Chemical protein polyubiquitination reveals the role of a noncanonical polyubiquitin chain in DNA damage tolerance.
abstract: 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).
authors.affiliation: Department of Chemistry and Biochemistry, 214A Drake Hall, University of Delaware , Newark, Delaware 19716, United States.
authors.forename: Kun
authors.initials: K
authors.lastname: Yang
authors.forename: Ping
authors.initials: P
authors.lastname: Gong
authors.forename: Parikshit
authors.initials: P
authors.lastname: Gokhale
authors.forename: Zhihao
authors.initials: Z
authors.lastname: Zhuang
mesh_terms: D004249:DNA Damage; D025821:Polyubiquitin / Q000737:chemistry*; D011506:Proteins / Q000737:chemistry*; D054875:Ubiquitination
chemical_list: D011506:Proteins; D025821:Polyubiquitin