Publications by authors named "K L Berkner"
Article Synopsis
- Gamma-glutamyl carboxylase (GGCX) is crucial for modifying vitamin K-dependent proteins by adding carboxyl groups, which is essential for their functions in blood clotting and bone health.
- Mutations in GGCX can lead to diseases such as vitamin K clotting factor deficiency and pseudoxanthoma elasticum-like diseases, but the mechanisms behind these mutations are not fully understood.
- This chapter discusses biochemical and cellular methods used to study GGCX's function and the impact of its mutations, highlighting the need for a balanced presence of various components and methodologies to fully understand the enzyme's activity.
Telomeres protect chromosome ends and are distinguished from DNA double-strand breaks (DSBs) by means of a specialized chromatin composed of DNA repeats bound by a multiprotein complex called shelterin. We investigated the role of telomere-associated proteins in establishing end-protection by studying viable mutants lacking these proteins. Mutants were studied using a Schizosaccharomyces pombe model system that induces cutting of a 'proto-telomere' bearing telomere repeats to rapidly form a new stable chromosomal end, in contrast to the rapid degradation of a control DSB.
View Article and Find Full Text PDFγ-Glutamyl carboxylase (GGCX) generates multiple carboxylated Glus (Glas) in vitamin K-dependent (VKD) proteins that are required for their functions. GGCX is processive, remaining bound to VKD proteins throughout multiple Glu carboxylations, and this study reveals the essentiality of processivity to VKD protein function. GGCX mutants (V255M and S300F) whose combined heterozygosity in a patient causes defective clotting and calcification were studied using a novel assay that mimics in vivo carboxylation.
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- Researchers created a more efficient library of barcoded insertion mutants to better understand gene function compared to traditional yeast haploid gene deletion libraries.
- Unlike deletion libraries, this new method captures a wider range of gene phenotypes, including those arising from partial gene function, and includes essential growth genes.
- The innovative approach utilized a three-dimensional pooling and multiplexed sequencing technique, successfully identifying 4,391 insertion mutations with significantly fewer sequencing efforts, making it a valuable resource for the Schizosaccharomyces pombe research community.
Vitamin K-dependent (VKD) proteins undergo an unusual post-translational modification, which is the conversion of specific Glu residues to carboxylated Glu (Gla). Gla generation is required for the activation of VKD proteins, and occurs in the endoplasmic reticulum during their secretion to either the cell surface or from the cell. The gamma-glutamyl carboxylase produces Gla using reduced vitamin K, which becomes oxygenated to vitamin K epoxide.
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