Ubiquitin mediates the physical and functional interaction between human DNA polymerases η and ι
| Autor: | Roger Woodgate, Eiji Ohashi, Mary P. McLenigan, Martha G. Bomar, Elena Curti, John P. McDonald, Justyna McIntyre, Brian S. Plosky, Antonio E. Vidal |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2012 |
| Předmět: |
DNA Replication
Models Molecular Binding Sites biology DNA synthesis Ubiquitin DNA replication DNA-Directed DNA Polymerase Genome Integrity Repair and Replication Molecular biology Proliferating cell nuclear antigen Cell biology Mutation DNA Polymerase iota Genetics biology.protein Ultraviolet light Monoubiquitination Humans Protein Interaction Domains and Motifs Binding site Polymerase |
| Zdroj: | Nucleic Acids Research |
| ISSN: | 1362-4962 0305-1048 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|