SUMO-1 possesses DNA binding activity

<p>Abstract</p> <p>Background</p> <p>Conjugation of small ubiquitin-related modifiers (SUMOs) is a frequent post-translational modification of proteins. SUMOs can also temporally associate with protein-targets via SUMO binding motifs (SBMs). Protein sumoylation has been identified as an important regulatory mechanism especially in the regulation of transcription and the maintenance of genome stability. The precise molecular mechanisms by which SUMO conjugation and association act are, however, not understood.</p> <p>Findings</p> <p>Using NMR spectroscopy and protein-DNA cross-linking experiments, we demonstrate here that SUMO-1 can specifically interact with dsDNA in a sequence-independent fashion. We also show that SUMO-1 binding to DNA can compete with other protein-DNA interactions at the example of the regulatory domain of Thymine-DNA Glycosylase and, based on these competition studies, estimate the DNA binding constant of SUMO1 in the range 1 mM.</p> <p>Conclusion</p> <p>This finding provides an important insight into how SUMO-1 might exert its activity. SUMO-1 might play a general role in destabilizing DNA bound protein complexes thereby operating in a bottle-opener way of fashion, explaining its pivotal role in regulating the activity of many central transcription and DNA repair complexes.</p

Risk of Dumping Syndrome after Sleeve Gastrectomy and Roux-en-Y Gastric Bypass: Early Results of a Multicentre Prospective Study

Background. Bariatric surgery is an important field of surgery. An important complication of bariatric surgery is dumping syndrome (DS). Aims. To evaluate the incidence of DS in patients undergoing bariatric surgery. Methods. 541 patients included from 5 nutrition and bariatric centers in France underwent either LSG or LRYGB. They were evaluated at 1 month (M1) and 6 months (M6) postoperatively by an interview and completion of a dumping syndrome questionnaire. Results. 268 patients underwent LSG (Group A) and 273 underwent LRYGB. From the LRYGB patients 229 had mechanical gastrojejunoanal anastomosis with 30 mm linear stapler (Group B) and 44 had manual (hand sewn) 15 mm gastrojejunal anastomosis (Group C). Overall incidence of DS was 8.5% at M1 and M6. In LSG group (Group A), only 4 patients (1.49%) reported episodes of DS at M1 and 3 (1.12%) at M6. In Group B, 41 patients (17.90%) reported episodes of DS at M1 and 43 (18.78%) at M6. Group C experienced one case (2.27%) of DS at M1 and none (0%) at M6. Conclusions. Patients undergoing LRYGB, especially with larger gastrojejunal anastomosis, are more prone to developing DS following surgery than patients undergoing LSG or LRYGB with calibrated manual anastomosis

Metabolic and Hormonal Changes After Laparoscopic Roux-en-Y Gastric Bypass and Sleeve Gastrectomy: a Randomized, Prospective Trial

BACKGROUND: The mechanisms of amelioration of glycemic control early after laparoscopic Roux-en-Y gastric bypass (LRYGB) or laparoscopic sleeve gastrectomy (LSG) are not fully understood. METHODS: In this prospective, randomized 1-year trial, outcomes of LRYGB and LSG patients were compared, focusing on possibly responsible mechanisms. Twelve patients were randomized to LRYGB and 11 to LSG. These non-diabetic patients were investigated before and 1 week, 3 months, and 12 months after surgery. A standard test meal was given after an overnight fast, and blood samples were collected before, during, and after food intake for hormone profiles (cholecystokinin (CCK), ghrelin, glucagon-like peptide 1 (GLP-1), peptide YY (PYY)). RESULTS: In both groups, body weight and BMI decreased markedly and comparably leading to an identical improvement of abnormal glycemic control (HOMA index). Post-surgery, patients had markedly increased postprandial plasma GLP-1 and PYY levels (p > 0.05) with ensuing improvement in glucose homeostasis. At 12 months, LRYGB ghrelin levels approached preoperative values. The postprandial, physiologic fluctuation returned, however, while LSG ghrelin levels were still markedly attenuated. One year postoperatively, CCK concentrations after test meals increased less in the LRYGB group than they did in the LSG group, with the latter showing significantly higher maximal CCK concentrations (p > 0.012 vs. LRYGB). CONCLUSIONS: Bypassing the foregut is not the only mechanism responsible for improved glucose homeostasis. The balance between foregut (ghrelin, CCK) and hindgut (GLP-1, PYY) hormones is a key to understanding the underlying mechanisms