Ubiquitin mediates the physical and functional interaction between human DNA polymerases η and ι

Justyna McIntyre, Antonio E. Vidal, Mary P. McLenigan, Martha G. Bomar, Elena Curti, John P. McDonald, Brian S. Plosky, Eiji Ohashi, Roger Woodgate

Research output: Contribution to journalArticle

17 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)1649-1660
Number of pages12
JournalNucleic acids research
Volume41
Issue number3
DOIs
Publication statusPublished - Feb 1 2013

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DNA-Directed DNA Polymerase
Ubiquitin
Ubiquitination
Proliferating Cell Nuclear Antigen
DNA
Ultraviolet Rays
Proteins

All Science Journal Classification (ASJC) codes

  • Genetics

Cite this

McIntyre, J., Vidal, A. E., McLenigan, M. P., Bomar, M. G., Curti, E., McDonald, J. P., ... Woodgate, R. (2013). Ubiquitin mediates the physical and functional interaction between human DNA polymerases η and ι. Nucleic acids research, 41(3), 1649-1660. https://doi.org/10.1093/nar/gks1277

Ubiquitin mediates the physical and functional interaction between human DNA polymerases η and ι. / McIntyre, Justyna; Vidal, Antonio E.; McLenigan, Mary P.; Bomar, Martha G.; Curti, Elena; McDonald, John P.; Plosky, Brian S.; Ohashi, Eiji; Woodgate, Roger.

In: Nucleic acids research, Vol. 41, No. 3, 01.02.2013, p. 1649-1660.

Research output: Contribution to journalArticle

McIntyre, J, Vidal, AE, McLenigan, MP, Bomar, MG, Curti, E, McDonald, JP, Plosky, BS, Ohashi, E & Woodgate, R 2013, 'Ubiquitin mediates the physical and functional interaction between human DNA polymerases η and ι', Nucleic acids research, vol. 41, no. 3, pp. 1649-1660. https://doi.org/10.1093/nar/gks1277
McIntyre J, Vidal AE, McLenigan MP, Bomar MG, Curti E, McDonald JP et al. Ubiquitin mediates the physical and functional interaction between human DNA polymerases η and ι. Nucleic acids research. 2013 Feb 1;41(3):1649-1660. https://doi.org/10.1093/nar/gks1277
McIntyre, Justyna ; Vidal, Antonio E. ; McLenigan, Mary P. ; Bomar, Martha G. ; Curti, Elena ; McDonald, John P. ; Plosky, Brian S. ; Ohashi, Eiji ; Woodgate, Roger. / Ubiquitin mediates the physical and functional interaction between human DNA polymerases η and ι. In: Nucleic acids research. 2013 ; Vol. 41, No. 3. pp. 1649-1660.
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