Open AccessUbiquitin mediates the physical and functional interaction between human DNA polymerases η and ι
Author(s) -
Justyna McIntyre,
Antonio E. Vidal,
Mary P. McLenigan,
Martha G. Bomar,
Elena Curti,
John P. McDonald,
Brian S. Plosky,
Eiji Ohashi,
Roger Woodgate
Publication year - 2012
Publication title -
nucleic acids research
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 9.008
H-Index - 537
eISSN - 1362-4954
pISSN - 0305-1048
DOI - 10.1093/nar/gks1277
Subject(s) - biology , dna polymerase , ubiquitin , proliferating cell nuclear antigen , polymerase , dna replication , dna polymerase delta , microbiology and biotechnology , processivity , genetics , dna , gene , rna , reverse transcriptase
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.