A conserved physical and functional interaction between the cell cycle checkpoint clamp loader and DNA ligase I of eukaryotes Journal Article
| Authors: | Song, W.; Levin, D. S.; Varkey, J.; Post, S.; Bermudez, V. P.; Hurwitz, J.; Tomkinson, A. E. |
| Article Title: | A conserved physical and functional interaction between the cell cycle checkpoint clamp loader and DNA ligase I of eukaryotes |
| Abstract: | DNA ligase I joins Okazaki fragments during DNA replication and completes certain excision repair pathways. The participation of DNA ligase I in these transactions is directed by physical and functional interactions with proliferating cell nuclear antigen, a DNA sliding clamp, and, replication factor C (RFC), the clamp loader. Here we show that DNA ligase I also interacts with the hRad17 subunit of the hRad17-RFC cell cycle checkpoint clamp loader, and with each of the subunits of its DNA sliding clamp, the heterotrimeric hRad9-hRad1-hHus1 complex. In contrast to the inhibitory effect of RFC, hRad17-RFC stimulates joining by DNA ligase I. Similar results were obtained with the homologous Saccharomyces cerevisiae proteins indicating that the interaction between the replicative DNA ligase and checkpoint clamp is conserved in eukaryotes. Notably, we show that hRad17 preferentially interacts with and specifically stimulates dephosphorylated DNA ligase I. Moreover, there is an increased association between DNA ligase I and hRad17 in S phase following DNA damage and replication blockage that occurs concomitantly with DNA damage-induced dephosphorylation of chromatin-associated DNA ligase I. Thus, our results suggest that the in vivo interaction between DNA ligase I and the checkpoint clamp loader is regulated by post-translational modification of DNA ligase I. © 2007 by The American Society for Biochemistry and Molecular Biology, Inc. |
| Keywords: | controlled study; human cell; dna-binding proteins; nonhuman; dna replication; protein function; protein analysis; cell cycle proteins; dna damage; cell cycle; cell cycle s phase; complex formation; protein protein interaction; hela cells; phosphorylation; nuclear proteins; dna; protein processing; cell culture; saccharomyces cerevisiae; eukaryota; intracellular signaling peptides and proteins; protein dephosphorylation; saccharomyces cerevisiae proteins; replication factor c; replication protein c; eukaryotic cell; polydeoxyribonucleotide synthase; cell cycle regulation; subcellular fractions; enzymes; complexation; dna ligases; chromatography, affinity; replication factors; cell cycles; dna ligase i; molecular interactions |
| Journal Title: | Journal of Biological Chemistry |
| Volume: | 282 |
| Issue: | 31 |
| ISSN: | 0021-9258 |
| Publisher: | American Society for Biochemistry and Molecular Biology |
| Date Published: | 2007-08-03 |
| Start Page: | 22721 |
| End Page: | 22730 |
| Language: | English |
| DOI: | 10.1074/jbc.M703774200 |
| PUBMED: | 17561505 |
| PROVIDER: | scopus |
| DOI/URL: | |
| Notes: | --- - "Cited By (since 1996): 11" - "Export Date: 17 November 2011" - "CODEN: JBCHA" - "Source: Scopus" |
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