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Zinc Finger Motif (zinc + finger_motif)
Selected AbstractsNovel germline BRCA1 and BRCA2 mutations in breast and breast/ovarian cancer families from the Czech Republic ,,HUMAN MUTATION, Issue 6 2001Eva Machackova Abstract Germline mutations in breast cancer susceptibility genes, BRCA1 and BRCA2, are responsible for a substantial proportion of high-risk breast and breast/ovarian cancer families. To characterize the spectrum of BRCA1 and BRCA2 mutations, we screened Czech families with breast/ovarian cancer using the non-radioactive protein truncation test, heteroduplex analysis and direct sequencing. In a group of 100 high-risk breast and breast/ovarian cancer families, four novel frame shift mutations were identified in BRCA1 and BRCA2 genes. In BRCA1, two novel frame shift mutations were identified as 3761-3762delGA and 2616-2617ins10; in BRCA2, two novel frame shift mutations were identified as 5073-5074delCT and 6866delC. Furthermore, a novel missense substitution M18K in BRCA1 gene in a breast/ovarian cancer family was identified which lies adjacent just upstream of the most highly conserved C3HC4 RING zinc finger motif. To examine the tertiary structure of the RING zinc finger domain and possible effects of M18K substitution on its stability, we used threading techniques according to the crystal structure of RAG1 dimerization domain of the DNA-binding protein. © 2000 Wiley-Liss, Inc. [source] Solution structure of the region 51,160 of human KIN17 reveals an atypical winged helix domainPROTEIN SCIENCE, Issue 12 2007Ludovic Carlier Abstract Human KIN17 is a 45-kDa eukaryotic DNA- and RNA-binding protein that plays an important role in nuclear metabolism and in particular in the general response to genotoxics. Its amino acids sequence contains a zinc finger motif (residues 28,50) within a 30-kDa N-terminal region conserved from yeast to human, and a 15-kDa C-terminal tandem of SH3-like subdomains (residues 268,393) only found in higher eukaryotes. Here we report the solution structure of the region 51,160 of human KIN17. We show that this fragment folds into a three-,-helix bundle packed against a three-stranded ,-sheet. It belongs to the winged helix (WH) family. Structural comparison with analogous WH domains reveals that KIN17 WH module presents an additional and highly conserved 310 -helix. Moreover, KIN17 WH helix H3 is not positively charged as in classical DNA-binding WH domains. Thus, human KIN17 region 51,160 might rather be involved in protein,protein interaction through its conserved surface centered on the 310 -helix. [source] BNR , a LINE family from Beta vulgaris, contains a RRM domain in open reading frame 1 and defines a L1 sub-clade present in diverse plant genomesTHE PLANT JOURNAL, Issue 6 2009Tony Heitkam Summary We characterized a novel type of plant non-LTR retrotransposons, identified as the BNR family, in sugar beet (Beta vulgaris) genomes. Although their ORF2 sequences were similar to those of previously analysed LINEs (long interspersed nuclear elements) of the L1 clade, their ORF1 sequences differ strongly from those of most plant LINEs. Two novel domains were identified, containing a conserved secondary motif, known as the RNA recognition motif (RRM). ORF1 lacks the zinc finger motif that is typical of plant LINEs, but has an RRM that is likely to have a RNA-binding function. BNR LINEs are highly diverse, and were characterized by gel-blot and fluorescent in situ hybridization, showing a widespread occurrence and clustering along chromosome arms. Insertion of BNR1 into a well-described satellite repeat was detected in two cultivars only, indicating recent activity. Database searches revealed the existence of LINE families possessing an ORF1 sequence similar to that of BNR in the genomes of higher plants such as poplar, lotus and soybean. Comparing their reverse transcriptase regions with those of other retrotransposons, these LINEs were assigned to the L1 clade, but form a distinct group, providing evidence of a major separation of L1 elements in plants. This indicates a common origin of BNR-like LINEs, suggesting that these elements form a sub-clade designated as the BNR sub-clade. [source] Functionally redundant SHI family genes regulate Arabidopsis gynoecium development in a dose-dependent mannerTHE PLANT JOURNAL, Issue 1 2006Sandra Kuusk Summary Gene duplication events, and the subsequent functional divergence of duplicates, are believed to be important evolutionary agents, driving morphological diversification. We have studied the structural and functional diversification of members of a plant-specific gene family in Arabidopsis thaliana by analysing mutant phenotypes, expression patterns and phylogeny. The SHI gene family comprises ten members that encode proteins with a RING finger-like zinc finger motif. We show that, despite being highly divergent in sequence, except in two conserved regions, many of the SHI -related genes are partially redundant in function and synergistically promote gynoecium, stamen and leaf development in Arabidopsis. Gynoecia of the loss-of-function sty1-1 mutant display subtle morphological defects, and, although mutations in the related STY2, SHI, SRS3, SRS4, SRS5, SRS7 and LRP1 genes have no apparent effect on gynoecium development, the sty1-1 mutant phenotype is gradually enhanced in double, triple, quadruple and quintuple mutant combinations, suggesting a remarkably extensive functional conservation within the family, which appears to be based on dosage dependency and protection against dominant negative mutations. In multiple mutant lines, all marginal tissues in the apical part of the gynoecium are dramatically reduced or missing, and our data indicate that SHI family members may promote formation of these tissues downstream of the transcriptional co-repressor LEUNIG (LUG). [source] Regulation of transcription of the Dnmt1 gene by Sp1 and Sp3 zinc finger proteinsFEBS JOURNAL, Issue 12 2002Shotaro Kishikawa The Sp family is a family of transcription factors that bind to cis -elements in the promoter regions of various genes. Regulation of transcription by Sp proteins is based on interactions between a GC-rich binding site (GGGCGG) in DNA and C-terminal zinc finger motifs in the proteins. In this study, we characterized the GC-rich promoter of the gene for the DNA methyltransferase (Dnmt1) that is responsible for methylation of cytosine residues in mammals and plays a role in gene silencing. We found that a cis -element (nucleotides ,161 to ,147) was essential for the expression of the mouse gene for Dnmt1. DNA-binding assays indicated that transcription factors Sp1 and Sp3 bound to the same cis -element in this region in a dose-dependent manner. In Drosophila SL2 cells, which lack the Sp family of transcription factors, forced expression of Sp1 or Sp3 enhanced transcription from the Dnmt1 promoter. Stimulation by Sp1 and Sp3 were independent phenomena. Furthermore, cotransfection reporter assays with a p300-expression plasmid revealed the activation of the promoter of the Dnmt1 gene in the presence of Sp3. The transcriptional coactivator p300 interacted with Sp3 in vivo and in vitro. Our results indicate that expression of the Dnmt1 gene is controled by Sp1 and Sp3 and that p300 is involved in the activation by Sp3. [source] | |||||||||||||