The kinetochore is an enhancer of pericentric cohesin binding.

The recruitment of cohesins to pericentric chromatin in some organisms appears to require heterochromatin associated with repetitive DNA. However, neocentromeres and budding yeast centromeres lack flanking repetitive DNA, indicating that cohesin recruitment occurs through an alternative pathway. Here, we demonstrate that all budding yeast chromosomes assemble cohesin domains that extend over 20-50 kb of unique pericentric sequences flanking the conserved 120-bp centromeric DNA. The assembly of these cohesin domains requires the presence of a functional kinetochore in every cell cycle. A similar enhancement of cohesin binding was also observed in regions flanking an ectopic centromere. At both endogenous and ectopic locations, the centromeric enhancer amplified the inherent levels of cohesin binding that are unique to each region. Thus, kinetochores are enhancers of cohesin association that act over tens of kilobases to assemble pericentric cohesin domains. These domains are larger than the pericentric regions stretched by microtubule attachments, and thus are likely to counter microtubule-dependent forces. Kinetochores mediate two essential segregation functions: chromosome movement through microtubule attachment and biorientation of sister chromatids through the recruitment of high levels of cohesin to pericentric regions. We suggest that the coordination of chromosome movement and biorientation makes the kinetochore an autonomous segregation unit.

The efficacy of supplemental magnesium in reducing atrial fibrillation after coronary artery bypass grafting.

BACKGROUND: Atrial fibrillation after coronary artery bypass is reported from 17% to 53%. Hypomagnesemia after this surgery is considered a contributing factor. METHODS: Two hundred-two coronary bypass patients were randomized to magnesium (n = 105) or placebo (n = 97). The experimental group received 80-mg magnesium sulfate per kilogram ideal weight in 100 mL dextrose 5% water 30 minutes preoperatively. Postoperatively, patients received 8-mg magnesium sulfate per kilogram ideal weight intravenous per hour more than 48 hours. The control group received dextrose 5% water at these intervals. RESULTS: After the first bolus serum magnesium was experimental 4.75 mg/dL versus control 1.91 mg/dL, p less than 0.001, and remained different until postoperative day 4 (experimental 2.33 mg/dL vs control 2.26 mg/dL, p = 0.24). Atrial appendage and strap muscle were analyzed after the first bolus and after revascularization. There were no differences between groups in tissue magnesium or calcium. Urinary magnesium was elevated in the experimental (experimental 324.5 mg/24 hours, vs control 45.1 mg/24 hours, p = 0.01). Calcium excretion was higher (experimental 370 mg/24 hours vs control 186 mg/24 hours, p < 0.001) and was associated with lower serum calcium. Serum calcium was higher in the control through the fourth postoperative day. The incidence of atrial fibrillation was experimental 32 of 105 (30.5%) versus control 41 of 97 (42.3%) p = 0.08. Atrial fibrillation was different on the first postoperative day (experimental 3/105, 2.9% vs control 9/97, 9.3%), p = 0.05. CONCLUSIONS: Overall prophylactic magnesium supplementation does not significantly reduce atrial and ventricular arrhythmias. The only significant benefit of magnesium supplementation was on the first postoperative day.