Integrated dialysis and renal transplantation: small is beautiful.

Many patients in Britain with chronic renal failure suitable for renal replacement treatment die because not enough treatment facilities are available. Moreover, the number of renal transplants performed is insufficient to meet even present needs, so the number of patients on dialysis is rising. The integrated dialysis and transplant unit in Aberdeen, which has a population base much smaller than the average British unit, meets community needs for dialysis and transplantation. The problem of harvesting cadaver kidneys has been solved; the present supply has not only enabled the number of patients on dialysis to remain stable but has resulted in a net export of kidneys. The Aberdeen unit shows how estimated needs for chronic dialysis and renal transplantation may be met.     

Reverse genetic analysis of the yeast RSC chromatin remodeler reveals a role for RSC3 and SNF5 homolog 1 in ploidy maintenance

The yeast “remodels the structure of chromatin” (RSC) complex is a multi-subunit “switching deficient/sucrose non-fermenting” type ATP-dependent nucleosome remodeler, with human counterparts that are well-established tumor suppressors. Using temperature-inducible degron fusions of all the essential RSC subunits, we set out to map RSC requirement as a function of the mitotic cell cycle. We found that RSC executes essential functions during G1, G2, and mitosis. Remarkably, we observed a doubling of chromosome complements when degron alleles of the RSC subunit SFH1, the yeast hSNF5 tumor suppressor ortholog, and RSC3 were combined. The requirement for simultaneous deregulation of SFH1 and RSC3 to induce these ploidy shifts was eliminated by knockout of the S-phase cyclin CLB5 and by transient depletion of replication origin licensing factor Cdc6p. Further, combination of the degron alleles of SFH1 and RSC3, with deletion alleles of each of the nine Cdc28/Cdk1-associated cyclins, revealed a strong and specific genetic interaction between the S-phase cyclin genes CLB5 and RSC3, indicating a role for Rsc3p in proper S-phase regulation. Taken together, our results implicate RSC in regulation of the G1/S-phase transition and establish a hitherto unanticipated role for RSC-mediated chromatin remodeling in ploidy maintenance.