title: Ubiquitin mediates the physical and functional interaction between human DNA polymerases η and ι.
abstract: Human DNA polymerases η and ι are best characterized for their ability to facilitate translesion DNA synthesis (TLS). Both polymerases (pols) co-localize in 'replication factories' in vivo after cells are exposed to ultraviolet light and this co-localization is mediated through a physical interaction between the two TLS pols. We have mapped the polη-ι interacting region to their respective ubiquitin-binding domains (UBZ in polη and UBM1 and UBM2 in polι), and demonstrate that ubiquitination of either TLS polymerase is a prerequisite for their physical and functional interaction. Importantly, while monoubiquitination of polη precludes its ability to interact with proliferating cell nuclear antigen (PCNA), it enhances its interaction with polι. Furthermore, a polι-ubiquitin chimera interacts avidly with both polη and PCNA. Thus, the ubiquitination status of polη, or polι plays a key regulatory function in controlling the protein partners with which each polymerase interacts, and in doing so, determines the efficiency of targeting the respective polymerase to stalled replication forks where they facilitate TLS.
authors.affiliation: Laboratory of Genomic Integrity, National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, MD 20892-3371, USA.
authors.forename: Justyna
authors.initials: J
authors.lastname: McIntyre
authors.forename: Antonio E
authors.initials: AE
authors.lastname: Vidal
authors.forename: Mary P
authors.initials: MP
authors.lastname: McLenigan
authors.forename: Martha G
authors.initials: MG
authors.lastname: Bomar
authors.forename: Elena
authors.initials: E
authors.lastname: Curti
authors.forename: John P
authors.initials: JP
authors.lastname: McDonald
authors.forename: Brian S
authors.initials: BS
authors.lastname: Plosky
authors.forename: Eiji
authors.initials: E
authors.lastname: Ohashi
authors.forename: Roger
authors.initials: R
authors.lastname: Woodgate
mesh_terms: D001665:Binding Sites; D004261:DNA Replication; D004259:DNA-Directed DNA Polymerase / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D008958:Models, Molecular; D009154:Mutation; D054730:Protein Interaction Domains and Motifs; D025801:Ubiquitin / Q000378:metabolism*; D000094769:DNA Polymerase iota; D000099270:Y-Family DNA Polymerases
chemical_list: D004259:DNA-Directed DNA Polymerase; D025801:Ubiquitin; D000094769:DNA Polymerase iota; C112338:Rad30 protein; D000099270:Y-Family DNA Polymerases; C000722070:POLI protein, human