However, RRM2(RxI/AxA), in which Thr33 is intact, was unable to bind cyclin F, even though phosphorylation of Thr33 was unaffected ( Figure 2C), and a peptide corresponding to amino acids 26–39 of RRM2 (i.e., a peptide that does not contain the CY motif) was unable to bind cyclin F irrespective of the Thr33 phosphorylation state ( Figure 2G). RRM2(T33A), which contains an intact CY motif, did not efficiently bind cyclin F in vivo or in vitro ( Figures 2C, 2F, and S2C), and wild-type RRM2 was unable to bind cyclin F in vitro without prior phosphorylation by a CDK ( Figure 2F). Graphical Abstractīoth Thr33 and the CY motif of RRM2 are highly conserved across species ( Figure S2D), and both are necessary, but not sufficient, for a stable binding of RRM2 to cyclin F. In summary, we have identified a biochemical pathway that controls the abundance of dNTPs and ensures efficient DNA repair in response to genotoxic stress. Defective elimination of cyclin F delays DNA repair and sensitizes cells to DNA damage, a phenotype that is reverted by expressing a nondegradable RRM2 mutant. After DNA damage, cyclin F is downregulated in an ATR-dependent manner to allow accumulation of RRM2. We found that, during G2, following CDK-mediated phosphorylation of Thr33, RRM2 is degraded via SCF cyclin F to maintain balanced dNTP pools and genome stability. Ribonucleotide reductase (RNR) catalyzes the conversion of ribonucleotides to deoxyribonucleotides (dNTPs), which are necessary for both replicative and repair DNA synthesis. Using affinity purifications and mass spectrometry, we identified RRM2 (the ribonucleotide reductase family member 2) as an interactor of the F-box protein cyclin F. It is this trust that makes owning a pool a positive experience for our customers, which is why we got into the pool servicing business in the first place.F-box proteins are the substrate binding subunits of SCF (Skp1-Cul1-F-box protein) ubiquitin ligase complexes. This builds trust, which is very important to us. We have experienced technicians to get your pool serviced or repaired the first time around. We take pride in the fact that we offer the best-in-class pool service and repairs with a personal touch our customers deserve. From working previously as a pool service technician or being on the receiving end of pool service, we know that not every pool maintenance company is the same. It should be fun, entertaining, and it is a big investment. When Robert started in the pool business, he found there was a lack of trust in the industry. Speaking of keeping up to date, we also stay on top of the latest chemical treatments to ensure that your pool stays healthy. We take out any complications that could occur by using the latest tools and automation software to help with communicate with you. As we are a family-owned business, it means that we treat every pool as we would our own family pool. We want you to feel like you are part of the Pool Refs family. That’s why we’ll always go above and beyond to help. This starts with ensuring that you are happy with the service we provide for you. Why do your neighbors choose us to help keep their pools in check?Īt Pool Referees, our number one goal is to help make your life easier.
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