Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:3.1.30.2 (endonuclease)
 18,621 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Sporadic fundic gland polyposis (SFGP) is defined as multiple fundic gland polyps in patients without familial adenomatous polyposis syndrome (FAP). Although little is known about the genetic changes in SFGP, mutations in the Wnt signaling pathway have been recently linked to fundic gland polyps in other settings: sporadic polyps are linked to activating beta-catenin mutations, whereas FAP-associated fundic gland polyps are caused by second somatic hits in the adenomatous polyposis coli gene. The relationship between SFGP, single sporadic fundic gland polyps, and FAP-associated polyps remains unclear, and SFGP remain poorly characterized at the clinical, histological, and molecular levels. A retrospective study was undertaken of eight patients with SFGP who had >/=10 polyps with at least five endoscopic biopsy specimens available for study. One additional patient with attenuated FAP who underwent partial gastrectomy was included as a control. The medical records and biopsy specimens were reviewed. Mutations of the beta-catenin gene were evaluated in each fundic gland as well as in control nonpolypoid tissue by direct sequencing of a mutational hot spot in exon 3 of the beta-catenin gene, which encodes the GSK-3beta phosphorylation sites, and a HinfI endonuclease digestion assay. The four men and four women in the study were an average of 57 years of age at biopsy. All patients were on acid-suppression therapy, 5/8 with proton-pump inhibitors (PPI) and 3/8 with Zantac. Sixty-two polyps were studied, and all were <10 mm, with most between 2 and 7 mm. The polyps were histologically identical to single sporadic fundic gland polyps. No dysplasia was seen. Forty-seven of 62 polyps (76%) had detectable beta-catenin mutations. Mutations were found in all eight of the patients. All were point mutations in codons 32, 33, 34, and 37 and are either phosphorylation sites or immediately adjacent to phosphorylation sites, findings identical to that seen in single sporadic fundic gland polyps. Each polyp had a single mutation, and each patient had more than one unique mutation (median = 4), indicating a multifocal origin for the polyps. No mutations were found in nonpolypoid control tissue and in polyps from the attenuated FAP patient. The patients with SFGP in this series were all between 40 and 70 years of age and had histories of acid-suppressive therapy. The fundic gland polyps were histologically and genetically identical to single sporadic fundic gland polyps and demonstrated frequent somatic activating mutations in exon 3 of the beta-catenin gene.
 ...
PMID:Sporadic fundic gland polyposis: a clinical, histological, and molecular analysis. 1211 9

Meiotic recombination is initiated by DNA double-stranded breaks introduced by the SPO11 protein. Despite a decade of research, the biochemical functions of SPO11 remain largely unknown, perhaps because of difficulties in studying the functionally active SPO11. Arabidopsis thaliana encodes three SPO11-related proteins, two of which (SPO11-1 and SPO11-2) are required for, and cooperate in, meiosis. We isolated soluble SPO11-1, fused with or free of a trigger factor-tag at its N terminus. The tag-free SPO11-1 needed to interact physically with soluble SPO11-1 to maintain its solubility, suggesting a multimeric active form including a solubilizing protein cofactor. An N-terminal fragment of PRD1, a SPO11-1-interacting protein required for normal meiosis, but not SPO11-2, forms a soluble complex with trigger factor-tagged SPO11-1, but the trigger factor-tag was required for the solubility. Formation of the complex is not sufficient to express endonuclease activity. Trigger factor-tagged SPO11-1 exhibited DNA-binding activities: Glu substitutions of the invariant Gly215 and Arg222 and of the nonconserved Arg223 and Arg226 in a conserved motif (G215E, R222E, R223E, R226E) reduced the DNA-binding ability in vitro, but substitutions of the conserved Arg130 and invariant Tyr103 (a residue in the putative endonuclease-active center) and of Arg residues outside conserved motifs by Glu or Phe (R130E, Y103F, R207E and R254E), did not. Tests for the ability of mutant spo11-1 proteins to complement the silique-defective phenotype of a spo11-1-homozygous mutant in vivo revealed that R222E and G215E induced serious deficiencies, while R130E caused a partial defect in silique formation. Thus, the Gly215, Arg222 and Arg223 residues of SPO11-1 form a DNA-binding surface that is functional in meiosis.
 ...
PMID:A DNA-binding surface of SPO11-1, an Arabidopsis SPO11 orthologue required for normal meiosis. 2042 61