ArticleCurrent biology : CB2012
Ribonucleotide reductase activity is coupled to DNA synthesis via proliferating cell nuclear antigen.
Article in Current biology : CB, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 15 papers.
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Who cites it
15 citing papers in PubMed, 28 citations in OpenAlex.
- Host factor SAMHD1 restricts DNA viruses in non-dividing myeloid cells.PLoS pathogens · 2013Trial
- Checkpoint activation by Spd1: a competition-based system relying on tandem disordered PCNA binding motifs.Nucleic acids research · 2024Article
- A context-dependent and disordered ubiquitin-binding motif.Cellular and molecular life sciences : CMLS · 2022Article
- CRL4Cdt2 ubiquitin ligase regulates Dna2 and Rad16 (XPF) nucleases by targeting Pxd1 for degradation.PLoS genetics · 2020Article
- The PCNA interaction motifs revisited: thinking outside the PIP-box.Cellular and molecular life sciences : CMLS · 2019Article
- An essential role for dNTP homeostasis following CDK-induced replication stress.Journal of cell science · 2019Article
- Single-molecule analysis reveals that DNA replication dynamics vary across the course of schizogony in the malaria parasite Plasmodium falciparum.Scientific reports · 2017Article
- Article
- Substrates and Inhibitors of SAMHD1.PloS one · 2017Article
- Genetic instability in budding and fission yeast-sources and mechanisms.FEMS microbiology reviews · 2015Review
- Deoxyribonucleotide metabolism, mutagenesis and cancer.Nature reviews. Cancer · 2015Review
- Hug1 is an intrinsically disordered protein that inhibits ribonucleotide reductase activity by directly binding Rnr2 subunit.Nucleic acids research · 2014Article
- Thymine DNA glycosylase is a CRL4Cdt2 substrate.The Journal of biological chemistry · 2014Article
- Spd1 accumulation causes genome instability independently of ribonucleotide reductase activity but functions to protect the genome when deoxynucleotide pools are elevated.Journal of cell science · 2013Article
- Sequential steps in DNA replication are inhibited to ensure reduction of ploidy in meiosis.Molecular biology of the cell · 2013Article
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8 authors at 3 institutions in 2 countries.
Funding
Abstract
Synthesis of deoxynucleoside triphosphates (dNTPs) is required for both DNA replication and DNA repair and is catalyzed by ribonucleotide reductases (RNR), which convert ribonucleotides to their deoxy forms [1, 2]. Maintaining the correct levels of dNTPs for DNA synthesis is important for minimizing the mutation rate [3-7], and this is achieved by tight regulation of RNR [2, 8, 9]. In fission yeast, RNR is regulated in part by a small protein inhibitor, Spd1, which is degraded in S phase and after DNA damage to allow upregulation of dNTP supply [10-12]. Spd1 degradation is mediated by the activity of the CRL4(Cdt2) ubiquitin ligase complex [5, 13, 14]. This has been reported to be dependent on modulation of Cdt2 levels, which are cell cycle regulated, peaking in S phase, and which also increase after DNA damage in a checkpoint-dependent manner [7, 13]. We show here that Cdt2 level fluctuations are not sufficient to regulate Spd1 proteolysis and that the key step in this event is the interaction of Spd1 with the polymerase processivity factor proliferating cell nuclear antigen (PCNA), complexed onto DNA. This mechanism thus provides a direct link between DNA synthesis and RNR regulation.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.