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Title: Structurally Distinct Ubiquitin- and Sumo-Modified PCNA: Implications for Their Distinct Roles in the DNA Damage Response

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. Here, 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. In conclusion, 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.
Authors:
 [1] ;  [2] ;  [2] ;  [3] ;  [4] ;  [3] ;  [3] ;  [4] ;  [5] ;  [2]
  1. Lawrence Berkeley National Lab. (LBNL), Berkeley, CA (United States)
  2. Georgia State Univ. Atlanta, GA (United States)
  3. Univ. of Delaware, Newark, DE (United States)
  4. Univ. of Iowa College of Medicine, Iowa City, IA (United States)
  5. Lawrence Berkeley National Lab. (LBNL), Berkeley, CA (United States); Scripps Research Inst., La Jolla, FL (United States); Skaggs Inst. for Chemmical Biology, La Jolla, CA (United States)
Publication Date:
Grant/Contract Number:
AC02-05CH112; MCB-1149521; P01 CA092584; R01 CA081967; MCB-0953764; R01 GM108027; R01GM105404; AC02-05CH11231
Type:
Published Article
Journal Name:
Structure
Additional Journal Information:
Journal Volume: 23; Journal Issue: 4; Journal ID: ISSN 0969-2126
Publisher:
Elsevier
Research Org:
Lawrence Berkeley National Lab. (LBNL), Berkeley, CA (United States)
Sponsoring Org:
USDOE Office of Science (SC), Biological and Environmental Research (BER) (SC-23)
Country of Publication:
United States
Language:
English
Subject:
60 APPLIED LIFE SCIENCES
OSTI Identifier:
1246527
Alternate Identifier(s):
OSTI ID: 1257840