Send to

Choose Destination
Structure. 2015 Apr 7;23(4):724-733. doi: 10.1016/j.str.2015.02.008. Epub 2015 Mar 12.

Structurally distinct ubiquitin- and sumo-modified PCNA: implications for their distinct roles in the DNA damage response.

Author information

Life Sciences Division, Lawrence Berkeley National Laboratory, Berkeley, CA, 94720 USA.
Department of Chemistry, Center for Diagnostics and Therapeutics, Georgia State University, Atlanta, Georgia 30302 USA.
Department of Chemistry and Biochemistry, University of Delaware, Newark, DE 19716 USA.
Department of Biochemistry, University of Iowa College of Medicine, Iowa City, IA 52242 USA.
Department of Molecular Biology, The Scripps Research Institute, La Jolla, CA, 92037 USA.
Skaggs Institute for Chemical Biology, La Jolla, CA, 92037 USA.
Contributed equally


Proliferating cell nuclear antigen (PCNA) is a pivotal replication protein, which also controls cellular responses to DNA damage. Posttranslational modification of PCNA by SUMO and ubiquitin modulate these responses. How the modifiers alter PCNA-dependent DNA repair and damage tolerance pathways is largely unknown. We used hybrid methods to identify atomic models of PCNAK107-Ub and PCNAK164-SUMO consistent with small-angle X-ray scattering data of these complexes in solution. We show that SUMO and ubiquitin have distinct modes of association to PCNA. Ubiquitin adopts discrete docked binding positions. By contrast, SUMO associates by simple tethering and adopts extended flexible conformations. These structural differences are the result of the opposite electrostatic potentials of SUMO and Ub. The unexpected contrast in conformational behavior of Ub-PCNA and SUMO-PCNA has implications for interactions with partner proteins, interacting surfaces accessibility, and access points for pathway regulation.

[Indexed for MEDLINE]
Free PMC Article

Supplemental Content

Full text links

Icon for Elsevier Science Icon for PubMed Central
Loading ...
Support Center