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| Proc. Natl. Acad. Sci. U.S.A. Apr (2008); 105(14):5361-6 | |
| Regulation of polymerase exchange between Poleta and Poldelta by monoubiquitination of PCNA and the movement of DNA polymerase holoenzyme- | |
| Zhuang Z, Johnson RE, Haracska L, Prakash L, Prakash S, Benkovic SJ | |
| Department of Chemistry, 414 Wartik Laboratory, Pennsylvania State University, University Park, PA 16802, USA- zzhuang@udel-edu | |
| Abstract: To ensure efficient and timely replication of genomic DNA, organisms in all three kingdoms of life possess specialized translesion DNA synthesis -TLS- polymerases -Pols- that tolerate various types of DNA lesions- It has been proposed that an exchange between the replicative DNA Pol and the TLS Pol at the site of DNA damage enables lesion bypass to occur- However, to date the molecular mechanism underlying this process is not fully understood- In this study, we demonstrated in a reconstituted system that the exchange of Saccharomyces cerevisiae Poldelta with Poleta requires both the stalling of the holoenzyme and the monoubiquitination of proliferating cell nuclear antigen -PCNA-- A moving Poldelta holoenzyme is refractory to the incoming Poleta- Furthermore, we showed that the Poleta C-terminal PCNA-interacting protein motif is required for the exchange process- We also demonstrated that the second exchange step to bring back Poldelta is prohibited when Lys-164 of PCNA is monoubiquitinated- Thus the removal of the ubiquitin moiety from PCNA is likely required for the reverse exchange step after the lesion bypass synthesis by Poleta- | |
| [PUBMED: 18385374] |   |
| Copyright © 2009, Tyers Lab, The Samuel Lunenfeld Research Institute, Mount Sinai Hospital, All Rights Reserved. |
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| BioGRID: A General Repository for Interaction Datasets. Chris Stark, Bobby-Joe Breitkreutz, Teresa Reguly, Lorrie Boucher, Ashton Breitkreutz, Mike Tyers. Nucleic Acids Res. Jan 1;34:D535-9. |