Abstract
DNA polymerase η is a Y family polymerase involved in translesion synthesis (TLS). Its action is initiated by simultaneous interaction between the PIP box in pol η and PCNA and between the UBZ in pol η and monoubiquitin attached to PCNA. Whereas monoubiquitination of PCNA is required for its interaction with pol η during TLS, we now show that monoubiquitination of pol η inhibits this interaction, preventing its functions in undamaged cells. Identification of monoubiquitination sites within pol η nuclear localization signal (NLS) led to the discovery that pol η NLS directly contacts PCNA, forming an extended pol η-PCNA interaction surface. We name this the PCNA-interacting region (PIR) and show that its monoubiquitination is downregulated by various DNA-damaging agents. We propose that this mechanism ensures optimal availability of nonubiquitinated, TLS-competent pol η after DNA damage. Our work shows how monoubiquitination can either positively or negatively regulate the assembly of a protein complex, depending on which substrates are targeted by ubiquitin.
Original language | English |
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Pages (from-to) | 396-407 |
Number of pages | 12 |
Journal | Molecular Cell |
Volume | 37 |
Issue number | 3 |
DOIs | |
Publication status | Published - 12-02-2010 |
Externally published | Yes |
All Science Journal Classification (ASJC) codes
- Molecular Biology
- Cell Biology