DNA ligase I is recruited to sites of DNA replication by an interaction with proliferating cell nuclear antigen: identification of a common targeting mechanism for the assembly of replication factories
| Autor: | Alessandra Montecucco, Giovanni Ciarrocchi, Min Soo Park, Rossella Rossi, Ronald K. Gary, Teresa A. Motycka, Antonello Villa, Giuseppe Biamonti, David S. Levin, Alan E. Tomkinson |
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| Přispěvatelé: | Montecucco, A, Rossi, R, Levin, D, Gary, R, Park, M, Motycka, T, Ciarrocchi, G, Villa, A, Biamonti, G, Tomkinson, A |
| Jazyk: | angličtina |
| Rok vydání: | 1998 |
| Předmět: |
DNA Replication
Saccharomyces cerevisiae Proteins DNA Ligases DNA polymerase II Recombinant Fusion Proteins DNA-Binding Protein Nuclear Localization Signals Molecular Sequence Data Eukaryotic DNA replication Biology DNA polymerase delta General Biochemistry Genetics and Molecular Biology Minor Histocompatibility Antigens DNA Ligase ATP Replication factor C Control of chromosome duplication Proliferating Cell Nuclear Antigen Humans Amino Acid Sequence Replication Protein C Molecular Biology Cell Line Transformed chemistry.chemical_classification Homeodomain Proteins DNA ligase Binding Sites General Immunology and Microbiology General Neuroscience DNA replication Binding Site Homeodomain Protein Repressor Protein Molecular biology DNA-Binding Proteins Repressor Proteins chemistry Proto-Oncogene Proteins c-bcl-2 biology.protein Origin recognition complex Nuclear Localization Signal Saccharomyces cerevisiae Protein Research Article Human Recombinant Fusion Protein |
| Popis: | In mammalian cells, DNA replication occurs at discrete nuclear sites termed replication factories. Here we demonstrate that DNA ligase I and the large subunit of replication factor C (RF-C p140) have a homologous sequence of approximately 20 amino acids at their N-termini that functions as a replication factory targeting sequence (RFTS). This motif consists of two boxes: box 1 contains the sequence IxxFF whereas box 2 is rich in positively charged residues. N-terminal fragments of DNA ligase I and the RF-C large subunit that contain the RFTS both interact with proliferating cell nuclear antigen (PCNA) in vitro. Moreover, the RFTS of DNA ligase I and of the RF-C large subunit is necessary and sufficient for the interaction with PCNA. Both subnuclear targeting and PCNA binding by the DNA ligase I RFTS are abolished by replacement of the adjacent phenylalanine residues within box 1. Since sequences similar to the RFTS/PCNA-binding motif have been identified in other DNA replication enzymes and in p21(CIP1/WAF1), we propose that, in addition to functioning as a DNA polymerase processivity factor, PCNA plays a central role in the recruitment and stable association of DNA replication proteins at replication factories. |
| Databáze: | OpenAIRE |
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