Cdt1 proteolysis is promoted by dual PIP degrons and is modulated by PCNA ubiquitylation
Cdt1 plays a critical role in DNA replication regulation by controlling licensing. In Metazoa, Cdt1 is regulated by CRL4Cdt2-mediated ubiquitylation, which is triggered by DNA binding of proliferating cell nuclear antigen (PCNA). We show here that fission yeast Cdt1 interacts with PCNA in vivo and t...
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| Veröffentlicht in: | Nucleic acids research 2011-08, Vol.39 (14), p.5978-5990 |
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| creator | Guarino, Estrella Shepherd, Marianne E. A. Salguero, Israel Hua, Hui Deegan, Rachel S. Kearsey, Stephen E. |
| description | Cdt1 plays a critical role in DNA replication regulation by controlling licensing. In Metazoa, Cdt1 is regulated by CRL4Cdt2-mediated ubiquitylation, which is triggered by DNA binding of proliferating cell nuclear antigen (PCNA). We show here that fission yeast Cdt1 interacts with PCNA in vivo and that DNA loading of PCNA is needed for Cdt1 proteolysis after DNA damage and in S phase. Activation of this pathway by ultraviolet (UV)-induced DNA damage requires upstream involvement of nucleotide excision repair or UVDE repair enzymes. Unexpectedly, two non-canonical PCNA-interacting peptide (PIP) motifs, which both have basic residues downstream, function redundantly in Cdt1 proteolysis. Finally, we show that poly-ubiquitylation of PCNA, which occurs after DNA damage, reduces Cdt1 proteolysis. This provides a mechanism for fine-tuning the activity of the CRL4Cdt2 pathway towards Cdt1, allowing Cdt1 proteolysis to be more efficient in S phase than after DNA damage. |
| doi_str_mv | 10.1093/nar/gkr222 |
| format | Article |
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Finally, we show that poly-ubiquitylation of PCNA, which occurs after DNA damage, reduces Cdt1 proteolysis. 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Unexpectedly, two non-canonical PCNA-interacting peptide (PIP) motifs, which both have basic residues downstream, function redundantly in Cdt1 proteolysis. Finally, we show that poly-ubiquitylation of PCNA, which occurs after DNA damage, reduces Cdt1 proteolysis. 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| source | Oxford Journals Open Access Collection; MEDLINE; DOAJ Directory of Open Access Journals; PubMed Central; Free Full-Text Journals in Chemistry |
| subjects | Amino Acid Motifs Amino Acid Sequence Cell Cycle Proteins - chemistry Cell Cycle Proteins - metabolism Chromatin - metabolism DNA Damage DNA, Fungal - metabolism DNA-Binding Proteins - chemistry DNA-Binding Proteins - metabolism Genome Integrity, Repair and Metazoa Molecular Sequence Data Proliferating Cell Nuclear Antigen - metabolism S Phase - genetics Schizosaccharomyces - genetics Schizosaccharomyces - metabolism Schizosaccharomyces - radiation effects Schizosaccharomyces pombe Schizosaccharomyces pombe Proteins - chemistry Schizosaccharomyces pombe Proteins - metabolism Ubiquitination Ultraviolet Rays |
| title | Cdt1 proteolysis is promoted by dual PIP degrons and is modulated by PCNA ubiquitylation |
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