https://ogma.newcastle.edu.au/vital/access/ /manager/Index en-au 5 https://ogma.newcastle.edu.au/vital/access/ /manager/Repository/uon:45052 MLH1, MSH2, MSH6 and PMS2 cause Lynch syndrome that implies an increased cancer risk, where colon and endometrial cancer are the most frequent. Identification of these pathogenic variants is important to identify endometrial cancer patients with inherited increased risk of new cancers, in order to offer them lifesaving surveillance. However, several other genes are also part of the MMR pathway. It is therefore relevant to search for variants in additional genes that may be associated with cancer risk by including all known genes involved in the MMR pathway. Next-generation sequencing was used to screen 22 genes involved in the MMR pathway in constitutional DNA extracted from full blood from 199 unselected endometrial cancer patients. Bioinformatic pipelines were developed for identification and functional annotation of variants, using several different software tools and custom programs. This facilitated identification of 22 exonic, 4 UTR and 9 intronic variants that could be classified according to pathogenicity. This study has identified several germline variants in genes of the MMR pathway that potentially may be associated with an increased risk for cancer, in particular endometrial cancer, and therefore are relevant for further investigation. We have also developed bioinformatics strategies to analyse targeted sequencing data, including low quality data and genomic regions outside of the protein coding exons of the relevant genes.]]> Wed 26 Oct 2022 11:45:52 AEDT ]]> https://ogma.newcastle.edu.au/vital/access/ /manager/Repository/uon:37473 Wed 13 Jan 2021 17:16:44 AEDT ]]> https://ogma.newcastle.edu.au/vital/access/ /manager/Repository/uon:30154 Wed 11 Apr 2018 11:04:38 AEST ]]> https://ogma.newcastle.edu.au/vital/access/ /manager/Repository/uon:41790 Wed 07 Feb 2024 18:05:12 AEDT ]]> https://ogma.newcastle.edu.au/vital/access/ /manager/Repository/uon:35953 G) as part of a common haplotype, in combination with different loss-of-function variants in trans. The intronic variant alters splicing, and together the biallelic mutations lead to cellular deficiency of Pol ε and delayed S-phase progression. In summary, we establish POLE as a second gene in which mutations cause IMAGe syndrome. These findings add to a growing list of disorders due to mutations in DNA replication genes that manifest growth restriction alongside adrenal dysfunction and/or immunodeficiency, consolidating these as replisome phenotypes and highlighting a need for future studies to understand the tissue-specific development roles of the encoded proteins.]]> Tue 21 Jan 2020 09:52:40 AEDT ]]> https://ogma.newcastle.edu.au/vital/access/ /manager/Repository/uon:41005 Thu 21 Jul 2022 10:51:15 AEST ]]> https://ogma.newcastle.edu.au/vital/access/ /manager/Repository/uon:35350 Thu 01 Aug 2019 16:09:05 AEST ]]> https://ogma.newcastle.edu.au/vital/access/ /manager/Repository/uon:10871 5000 bp per second—and is powerful enough to remove other proteins from the DNA. In bacteria it is localised to the site of cell division, the septum, where it functions as a DNA pump at the late stages of the cell cycle, to expedite cytokinesis and chromosome segregation. The N terminus of the protein is involved in the cell-cycle-specific localisation and assembly of the cell-division machinery, whereas the C terminus forms the motor. The motor portion of FtsK has been studied by a combination of biochemistry, genetics, X-ray crystallography and single-molecule mechanical assays, and these will be the focus here. The motor can be divided into three subdomains: α, β and γ. The α and β domains multimerise to produce a hexameric ring with a central channel for dsDNA, and contain a RecA-like nucleotide-binding/hydrolysis fold. The motor is given directionality by the regulatory γ domain, which binds to polarised chromosomal sequences—5′-GGGNAGGG-3′, known as KOPS—to ensure that the motor is loaded onto DNA in a specific orientation such that subsequent translocation is always towards the region of the chromosome where replication usually terminates (the terminus), and specifically to the 28 bp dif site, located in this region. Once the FtsK translocase has located the dif site it then interacts with the XerCD site-specific recombinases to activate recombination.]]> Sat 24 Mar 2018 08:14:31 AEDT ]]> https://ogma.newcastle.edu.au/vital/access/ /manager/Repository/uon:33836 Mon 23 Sep 2019 12:48:27 AEST ]]>