title: Crystal structure of human REV7 in complex with a human REV3 fragment and structural implication of the interaction between DNA polymerase zeta and REV1.
abstract: DNA polymerase zeta (Polzeta) is an error-prone DNA polymerase involved in translesion DNA synthesis. Polzeta consists of two subunits: the catalytic REV3, which belongs to B family DNA polymerase, and the noncatalytic REV7. REV7 also interacts with REV1 polymerase, which is an error-prone Y family DNA polymerase and is also involved in translesion DNA synthesis. Cells deficient in one of the three REV proteins and those deficient in all three proteins show similar phenotype, indicating the functional collaboration of the three REV proteins. REV7 interacts with both REV3 and REV1 polymerases, but the structure of REV7 or REV3, as well as the structural and functional basis of the REV1-REV7 and REV3-REV7 interactions, remains unknown. Here we show the first crystal structure of human REV7 in complex with a fragment of human REV3 polymerase (residues 1847-1898) and reveal the mechanism underlying REV7-REV3 interaction. The structure indicates that the interaction between REV7 and REV3 creates a structural interface for REV1 binding. Furthermore, we show that the REV7-mediated interactions are responsible for DNA damage tolerance. Our results highlight the function of REV7 as an adapter protein to recruit Polzeta to a lesion site. REV7 is alternatively called MAD2B or MAD2L2 and also involved in various cellular functions such as signal transduction and cell cycle regulation. Our results will provide a general structural basis for understanding the REV7 interaction.
authors.affiliation: Graduate School of Nanobioscience, Yokohama City University, Tsurumi-ku, Yokohama 230-0045, Japan.
authors.forename: Kodai
authors.initials: K
authors.lastname: Hara
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Hashimoto
authors.forename: Yoshiki
authors.initials: Y
authors.lastname: Murakumo
authors.forename: Shunsuke
authors.initials: S
authors.lastname: Kobayashi
authors.forename: Toshiaki
authors.initials: T
authors.lastname: Kogame
authors.forename: Satoru
authors.initials: S
authors.lastname: Unzai
authors.forename: Satoko
authors.initials: S
authors.lastname: Akashi
authors.forename: Shunichi
authors.initials: S
authors.lastname: Takeda
authors.forename: Toshiyuki
authors.initials: T
authors.lastname: Shimizu
authors.forename: Mamoru
authors.initials: M
authors.lastname: Sato
mesh_terms: D000595:Amino Acid Sequence; D002460:Cell Line; D018360:Crystallography, X-Ray; D004249:DNA Damage; D004268:DNA-Binding Proteins / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism*; D004259:DNA-Directed DNA Polymerase / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D066298:In Vitro Techniques; D064246:Mad2 Proteins; D008954:Models, Biological; D008958:Models, Molecular; D008969:Molecular Sequence Data; D046912:Multiprotein Complexes; D009687:Nuclear Proteins / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism*; D009713:Nucleotidyltransferases / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism*; D010446:Peptide Fragments / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D054730:Protein Interaction Domains and Motifs; D021122:Protein Subunits; D011506:Proteins / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism*; D011994:Recombinant Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D017386:Sequence Homology, Amino Acid; D000099270:Y-Family DNA Polymerases
chemical_list: D004268:DNA-Binding Proteins; D004259:DNA-Directed DNA Polymerase; D064246:Mad2 Proteins; D046912:Multiprotein Complexes; D009687:Nuclear Proteins; D009713:Nucleotidyltransferases; D010446:Peptide Fragments; D021122:Protein Subunits; D011506:Proteins; D011994:Recombinant Proteins; C120552:MAD2L2 protein, human; C425929:DNA polymerase zeta; C429004:REV1 protein, human; D000099270:Y-Family DNA Polymerases; C118285:REV3L protein, human