High fat density, an indirect marker of fat quality, is associated with the propensity to store fat viscerally vs subcutaneously and is jointly characterized by an increased burden of CVD risk factors.

Structural maintenance of chromosomes (SMC) complexes and DNA topoisomerases are major determinants of chromosome structure and dynamics. The cohesin complex embraces sister chromatids throughout interphase, but during mitosis most cohesin is stripped from chromosome arms by early prophase, while the remaining cohesin at kinetochores is cleaved at anaphase. This two-step removal of cohesin is required for sister chromatids to separate. The cohesin-related Smc5/6 complex has been studied mostly as a determinant of DNA repair via homologous recombination. However, chromosome segregation fails in Smc5/6 null mutants or cells treated with small interfering RNAs. This also occurs in Smc5/6 hypomorphs in the fission yeast Schizosaccharomyces pombe following genotoxic and replication stress, or topoisomerase II dysfunction, and these mitotic defects are due to the postanaphase retention of cohesin on chromosome arms. Here we show that mitotic and repair roles for Smc5/6 are genetically separable in S. pombe. Further, we identified the histone variant H2A.Z as a critical factor to modulate cohesin dynamics, and cells lacking H2A.Z suppress the mitotic defects conferred by Smc5/6 dysfunction. Together, H2A.Z and the SMC complexes ensure genome integrity through accurate chromosome segregation. Chromosomal integrity is essential for normal growth and development. In eukaryotes, there are three essential complexes of proteins that are central to chromosome dynamics. These are cohesin, condensin, and the Smc5/6 complex, known collectively as the structural maintenance of chromosomes (SMC) complex. Each complex shares a related architecture, and central to them are a heterodimer of SMC proteins: Smc1 and -3 in cohesin, Smc2 and -4 in condensin, and Smc5 and -6 in Smc5/6. These SMC proteins are large coiled-coil molecules with globular N and C termini containing Walker A and B ATP-binding motifs. They fold and interact at a flexible hinge, with ATP acting to hold the globular domains together. A kleisin protein bridges each heterodimer to form a putative ring-shaped structure, and each complex has specific additional non-SMC proteins that serve as regulators and effectors of function (1-3).Chromosome condensation and sister chromatid cohesion are the key roles for condensin and cohesin, respectively (1). However, defects in DNA repair have also been described for yeast strains harboring hypomorphic mutant alleles of condensin (4) and cohesin (5-7) subunits. In the case of cohesin, a role in DNA repair could stem from the fact that DNA repair by homologous recombination (HR) requires the sister chromatid to be in close proximity to the damaged chromatid. However, more recently cohesin in mammalian cells has been shown to also act as a transcriptional insulator in collaboration with CTCF (8, 9), and so the DNA repair function of cohesin may be more complex than a simple scaffolding mechanism. As its name suggests, deciphering Smc5/6 function has proved more elusive, though most studies have focused on a role for this complex in...

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Isometric growth of larval insect midgut predicts that the ratio of midgut surface area to body mass decreases as larvae grow. Gut tissue and gut content masses were measured in first through fifth instar Manduca sexta larvae. Wet mass of gut tissue increased in relationship to body mass with a scaling exponent of 0.85 compared to an exponent of 1.33 for gut content mass, suggesting that surface area becomes increasingly limiting in larger larvae. To test the hypothesis that compensation for the decrease in relative surface area of the midgut occurs by increased expression of membrane proteins, we compared midgut mRNA expression in fourth and fifth instar. Surveyed genes encoded apical membrane proteins with diverse functions, including the potassium amino acid transporter KAAT1, ion channel CAATCH1, aminopeptidase msAPN3, V-type H-ATPase E subunit, and cation chloride cotransporter masBSC. KAAT1 was expressed 300- to 1500-fold higher in middle and posterior midgut compared to anterior midgut. Expression of msAPN3 was approximately 200-fold higher in posterior midgut than middle midgut. Expression of KAAT1 was 2.3- to 3.1-fold higher in fifth compared to fourth-instar larvae, and masBSC expression was 1.3- to 1.9-fold higher in fifth-instar larvae. Expression of msAPN3 and V-ATPase, but not KAAT1, decreased as body mass increased within the fifth instar. Although the increased expression of KAAT1 and masBSC in fifth-instar larvae supports the hypothesis of increased membrane protein expression in larger larvae, results from the other genes do not support this hypothesis.