S. coelicolor uses an active chromosome partitioning system for developmentally-regulated genome segregation, which is associated with spore formation. There are four known trans-acting segregation proteins (ParA, ParB, ParJ and Scy) and cis-acting centromere-like sites (parS). parA encodes a Walker-type ATPase that is required for efficient DNA segregation and proper placement of the ParB-parS nucleoprotein complexes. A paralogue of ParA is encoded by the S. coelicolor genome, SCO1772 (named ParH), that has 45% identical residues to ParA. In S. coelicolor aerial hyphae, a ∆parH mutant produces 5% of anucleate spores. In this study, ParH was identified as a novel interaction partner of S. coelicolor ParB. However, a Walker A motif K99E substitution in ParH and removal an N-terminal extension in ParH impaired interaction between ParH and ParB, as judged by bacterial two-hybrid analyses. ParH-EGFP localization resembles the evenly-spaced localization pattern of ParH-EGFP in aerial hyphae, which might suggest that ParH colocalizes with ParB. A parH-null mutant appears to be unable to properly organize the oriC regions within a subset of prespores, as judged by ParB-EGFP foci. In this study, through a random chromosomal library screening, a novel protein that interacts with ParA and ParH was also identified. HaaA (ParH and ParA Associated protein A) is required for proper chromosome segregation and is one of the 24 signature proteins of the Actinomycetes that are not found in other bacterial lineages. A bacterial two-hybrid analysis showed that HaaA interacts with itself and interaction between ParH and ParA was through the C-terminal unstructured region. Interaction between HaaA and ParA and ParA-like proteins was conserved in other Actinomycetes, such as S. venezuelae, C. glutamicum and M. smegmatis. There was no evidence for interaction with other tested segregation proteins. In addition, a haaA insertion-deletion mutant strain revealed that loss of HaaA affected chromosome segregation (6% anucleate spores) and HaaA-EGFP localizes within spores of the mature spore chains. Together these data revealed new information to further understand chromosome segregation in S. coelicolor. / Bayer School of Natural and Environmental Sciences; / Biological Sciences / PhD; / Dissertation;

No description available.

Chromosomų struktūros persitvarkymai gali lemti įvairius žmogaus sveikatos sutrikimus. Netgi chromosominės ligos, pvz., Dauno ar Ternerio sindromai, gali būti nulemtos ne chromosomų skaičiaus, bet chromosomų struktūros persitvarkymų. Chromosomų trūkiai gali vykti bet kurioje chromosomos dalyje, tai lemia įvairius chromosomų struktūros pokyčius, tačiau tik dalis jų yra suderinami su gyvybinėmis funkcijomis ir yra nustatomi postnataliai. Chromosomų struktūros persitvarkymai, priklausomai nuo to, subalansuoti ar nesubalansuoti, lemia įvairias dismorfines anomalijas arba vaisingumo problemas. Jų nustatymas yra svarbus genetiniam konsultavimui. Šio drabo tikslas- įvertinti chromosomų struktūros persitvarkymų, nustatytų VUL SK MGC 2002 – 2008 m., įvairovę ir genetinę jų reikšmę. Tam, kad būtų įvertinta chromosomų struktūros persitvarkymų įvairovę, buvo analizuojami 2002-2008 metais atlikti kariotipo tyrimai. Remiantis rezultatais galima teigti, kad dažniausias chromosomų struktūros pakitimas yra reciprokinė translokacija, kuri dažniausiai lemia nevaisingumą bei savaiminius persileidimus. Didžiausia chromosomų struktūros pakitimų įvairovė nustatyta X chromosomoje.Rutininė citogenetinė kariotipo analizė yra svarbi ir tais atvejais, kai atliekamas FISH tyrimas naudojant tam tikrai genetinei sričiai specifinį žymenį, kadangi skirtingi chromosomų struktūros persitvarkymai gali lemti panašų fenotipą. / Chromosome structural rearrangements could cause various human health problems. Even Down’s or Turner’s syndromes, which are usually determined by chromosome number change, in some cases could be caused by chromosome structure abnormalities. Structure rerrangements of autosomes, depending on whether it is balanced origin or not, are responsible for various dysmorphic abnormalities or fertility problems. Chromosome breakpoints can occur in any part of chromosome and form any type of rearrangement, but only part of them could be compatible with vital functions and detected postnatally. Chromosome structural rearrangements in many cases are unique and only particular ones are more common. The objective of this work was to assess the diversity of chromosome structural rearrangements and their implication to the human genetic. Cytogenetic analysis of karyotype was performed using G-banding and FISH techniques. Cytogenetic analyses of 76 patients using routine cytogenetic analysis and 20 patients using FISH method have been performed. In order to assess the variety of chromosome structural rearrangements, the results of karyotype analyses performed in Department of Human and Medical Genetics, Faculty of Medicine, Vilnius University during the period of 2002–2008 were reviewed. On the basis of obtained results a conclusion can be drawn that translocation is the most frequent chromosome structure rearrangement type, comprising 44,3% of all our cases. X chromosome is the most... [to full text]

Diss. (sammanfattning) Stockholm : Karol. inst. / Härtill 5 uppsatser.

Diss. (sammanfattning) Stockholm : Karol. inst. / Härtill 7 uppsatser.

Diss. (sammanfattning) Stockholm : Karol. inst. / Härtill 5 uppsatser.

Diss. (sammanfattning) Stockholm : Karol. inst. / Härtill 5 uppsatser.

Diss. (sammanfattning) Stockholm : Karol. inst. / Härtill 5 uppsatser.

Abstract . A draft of the whole human genomic sequence has been completed and published in 2001. Researches on structural genomics, functional genomics, proteomics, evolutionary and medical sciences have just begun since. The existence of ninety percent repetitive, non-coding sequences in the human genome and in other mammalian species as well, indicating some potential but unaware functions of these repetitive regions within the mammalian genomes remained to be discovered. Among all features in the genomic sequences, microsatellite has been characterized as one type of short tandem repeats (STRs), abundant in the human genome, which potentially plays some important roles in biological processes, such as makers for molecular biology, the enhancers for transcription, and protein-binding sites. Changes on microsatellite copy numbers also involve in the cause of a couple of diseases have been reported. The sequence of human chromosome 20 has been finished in Dec. 2001, which provided us a valuable resource to study about gene density and the distribution of repetitive sequences such as microsatellties as well. To build a more detail chromosome 20 microsatellite map, including di-, tri- and tetra-nucleotide microsatellites, we therefore designed a sequence-based, molecular markers discovery system by bioinformatics approaches. The results indicate that these repetitive sequences distribute across the chromosome 20 evenly. We further analyzed the GC content of the human chromosome 20. A comparison of GC content, microsatellite distribution and gene density of each contig shows some correlation among them. The slippage rates of di-nucleotide microsatellite were predicted by the formula basing on Markov Chain. Some interesting results were found in this thesis. The same approaches were applied on human chromosome 14, which was being completed sequencing in Feb. 2003. The results implied that our strategies might be useful in the advanced genetic studied or medicine researches.

published_or_final_version / Medical Sciences / Master / Master of Medical Sciences