title: Structurally distinct ubiquitin- and sumo-modified PCNA: implications for their distinct roles in the DNA damage response.
abstract: 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.
authors.affiliation: Life Sciences Division, Lawrence Berkeley National Laboratory, Berkeley, CA, 94720 USA.
authors.forename: Susan E
authors.initials: SE
authors.lastname: Tsutakawa
authors.affiliation: Department of Chemistry, Center for Diagnostics and Therapeutics, Georgia State University, Atlanta, Georgia 30302 USA.
authors.forename: Chunli
authors.initials: C
authors.lastname: Yan
authors.affiliation: Department of Chemistry, Center for Diagnostics and Therapeutics, Georgia State University, Atlanta, Georgia 30302 USA.
authors.forename: Xiaojun
authors.initials: X
authors.lastname: Xu
authors.affiliation: Department of Chemistry and Biochemistry, University of Delaware, Newark, DE 19716 USA.
authors.forename: Christopher P
authors.initials: CP
authors.lastname: Weinacht
authors.affiliation: Department of Biochemistry, University of Iowa College of Medicine, Iowa City, IA 52242 USA.
authors.forename: Bret D
authors.initials: BD
authors.lastname: Freudenthal
authors.affiliation: Department of Chemistry and Biochemistry, University of Delaware, Newark, DE 19716 USA.
authors.forename: Kun
authors.initials: K
authors.lastname: Yang
authors.affiliation: Department of Chemistry and Biochemistry, University of Delaware, Newark, DE 19716 USA.
authors.forename: Zhihao
authors.initials: Z
authors.lastname: Zhuang
authors.affiliation: Department of Biochemistry, University of Iowa College of Medicine, Iowa City, IA 52242 USA.
authors.forename: M Todd
authors.initials: MT
authors.lastname: Washington
authors.affiliation: Life Sciences Division, Lawrence Berkeley National Laboratory, Berkeley, CA, 94720 USA.|Department of Molecular Biology, The Scripps Research Institute, La Jolla, CA, 92037 USA.|Skaggs Institute for Chemical Biology, La Jolla, CA, 92037 USA.
authors.forename: John A
authors.initials: JA
authors.lastname: Tainer
authors.affiliation: Department of Chemistry, Center for Diagnostics and Therapeutics, Georgia State University, Atlanta, Georgia 30302 USA.
authors.forename: Ivaylo
authors.initials: I
authors.lastname: Ivanov
mesh_terms: D000595:Amino Acid Sequence; D004249:DNA Damage; D004260:DNA Repair; D056004:Molecular Dynamics Simulation; D008969:Molecular Sequence Data; D018809:Proliferating Cell Nuclear Antigen / Q000737:chemistry* / Q000378:metabolism; D011485:Protein Binding; D025842:SUMO-1 Protein / Q000737:chemistry / Q000378:metabolism*; D012441:Saccharomyces cerevisiae / Q000737:chemistry / Q000201:enzymology; D029701:Saccharomyces cerevisiae Proteins / Q000737:chemistry* / Q000378:metabolism; D058207:Sumoylation
chemical_list: D018809:Proliferating Cell Nuclear Antigen; D025842:SUMO-1 Protein; D029701:Saccharomyces cerevisiae Proteins