title: DNA polymerase δ and ζ switch by sharing accessory subunits of DNA polymerase δ.
abstract: Translesion DNA synthesis is an important branch of the DNA damage tolerance pathway that assures genomic integrity of living organisms. The mechanisms of DNA polymerase (Pol) switches during lesion bypass are not known. Here, we show that the C-terminal domain of the Pol ζ catalytic subunit interacts with accessory subunits of replicative DNA Pol δ. We also show that, unlike other members of the human B-family of DNA polymerases, the highly conserved and similar C-terminal domains of Pol δ and Pol ζ contain a [4Fe-4S] cluster coordinated by four cysteines. Amino acid changes in Pol ζ that prevent the assembly of the [4Fe-4S] cluster abrogate Pol ζ function in UV mutagenesis. On the basis of these data, we propose that Pol switches at replication-blocking lesions occur by the exchange of the Pol δ and Pol ζ catalytic subunits on a preassembled complex of accessory proteins retained on DNA during translesion DNA synthesis.
authors.affiliation: Eppley Institute for Research in Cancer and Allied Diseases, University of Nebraska Medical Center, Omaha, Nebraska 68198.
authors.forename: Andrey G
authors.initials: AG
authors.lastname: Baranovskiy
authors.affiliation: Eppley Institute for Research in Cancer and Allied Diseases, University of Nebraska Medical Center, Omaha, Nebraska 68198.
authors.forename: Artem G
authors.initials: AG
authors.lastname: Lada
authors.affiliation: Eppley Institute for Research in Cancer and Allied Diseases, University of Nebraska Medical Center, Omaha, Nebraska 68198.
authors.forename: Hollie M
authors.initials: HM
authors.lastname: Siebler
authors.affiliation: Eppley Institute for Research in Cancer and Allied Diseases, University of Nebraska Medical Center, Omaha, Nebraska 68198.
authors.forename: Yinbo
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: Eppley Institute for Research in Cancer and Allied Diseases, University of Nebraska Medical Center, Omaha, Nebraska 68198.
authors.forename: Youri I
authors.initials: YI
authors.lastname: Pavlov
authors.affiliation: Eppley Institute for Research in Cancer and Allied Diseases, University of Nebraska Medical Center, Omaha, Nebraska 68198. Electronic address: ttahirov@unmc.edu.
authors.forename: Tahir H
authors.initials: TH
authors.lastname: Tahirov
mesh_terms: D004257:DNA Polymerase II / Q000235:genetics / Q000378:metabolism*; D004258:DNA Polymerase III / Q000235:genetics / Q000378:metabolism*; D004261:DNA Replication / Q000502:physiology* / Q000528:radiation effects; D006801:Humans; D016296:Mutagenesis / Q000528:radiation effects; D000075223:Poly-ADP-Ribose Binding Proteins; D017434:Protein Structure, Tertiary; D014466:Ultraviolet Rays
chemical_list: D000075223:Poly-ADP-Ribose Binding Proteins; C434055:POLD1 protein, human; D004257:DNA Polymerase II; D004258:DNA Polymerase III; C119525:POLE protein, human