Tramentozzi, E., Ferraro, P., Hossain, M., Stillman, B., Bianchi, V., Pontarin, G. (July 2018) The dNTP triphosphohydrolase activity of SAMHD1 persists during S-phase when the enzyme is phosphorylated at T592. Cell Cycle, 17 (9). pp. 1102-1114. ISSN 1551-4005
Abstract
SAMHD1 is the major catabolic enzyme regulating the intracellular concentrations of DNA precursors (dNTPs). The S-phase kinase CDK2-cyclinA phosphorylates SAMHD1 at Thr-592. How this modification affects SAMHD1 function is highly debated. We investigated the role of endogenous SAMHD1 phosphorylation during the cell cycle. Thr-592 phosphorylation occurs first at the G1/S border and is removed during mitotic exit parallel with Thr-phosphorylations of most CDK1 targets. Differential sensitivity to the phosphatase inhibitor okadaic acid suggested different involvement of the PP1 and PP2 families dependent upon the time of the cell cycle. SAMHD1 turn-over indicates that Thr-592 phosphorylation does not cause rapid protein degradation. Furthermore, SAMHD1 influenced the size of the four dNTP pools independently of its phosphorylation. Our findings reveal that SAMHD1 is active during the entire cell cycle and performs an important regulatory role during S-phase by contributing with ribonucleotide reductase to maintain dNTP pool balance for proper DNA replication.
| Item Type: | Paper |
|---|---|
| Uncontrolled Keywords: | Deoxynucleotide metabolism Sterile alpha motif and HD domain containing protein1 (SAMHD1) cell cycle |
| Subjects: | bioinformatics > genomics and proteomics > genetics & nucleic acid processing > protein structure, function, modification > protein types > enzymes > kinase > CDK organs, tissues, organelles, cell types and functions > cell types and functions > cell functions > cell cycle bioinformatics > genomics and proteomics > genetics & nucleic acid processing > protein structure, function, modification > protein expression > phosphorylation |
| CSHL Authors: | |
| Communities: | CSHL Cancer Center Program > Gene Regulation and Inheritance Program CSHL labs > Stillman lab |
| Highlight: | Stillman, Bruce W. |
| Depositing User: | Matthew Dunn |
| Date: | 24 July 2018 |
| Date Deposited: | 26 Jul 2018 15:29 |
| Last Modified: | 14 Dec 2020 21:48 |
| PMCID: | PMC6110608 |
| Related URLs: | |
| URI: | https://repository.cshl.edu/id/eprint/37050 |
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