Biology subjects

Zawadzka, K.

Publications and source records attributed to Zawadzka, K..

3 recordsLinked to original sources

bioRxiv2021

The Thousand Polish Genomes Project- a national database of Polish variant allele frequencies

Although Slavic populations account for over 3.5% of world inhabitants, no centralized, open source reference database of genetic variation of any Slavic population exists to date. Such data are crucial for either biomedical research and genetic counseling and are essential for archeological and historical studies. Polish population, homogenous and sedentary in its nature but influenced by many migrations of the past, is unique and could serve as a good genetic reference for middle European Slavic nations. The aim of the present study was to describe first results of analyses of a newly created national database of Polish genomic variant allele frequencies. Never before has any study on the whole genomes of Polish population been conducted on such a large number of individuals (1,079). A wide spectrum of genomic variation was identified and genotyped, such as small and structural variants, runs of homozygosity, mitochondrial haplogroups and Mendelian inconsistencies. The allele frequencies were calculated for 943 unrelated individuals and released publicly as The Thousand Polish Genomes database. A precise detection and characterisation of rare variants enriched in the Polish population allowed to confirm the allele frequencies for known pathogenic variants in diseases, such as Smith-Lemli-Opitz syndrome (SLOS) or Nijmegen breakage syndrome (NBS). Additionally, the analysis of OMIM AR genes led to the identification of 22 genes with significantly different cumulative allele frequencies in the Polish (POL) vs European NFE population. We hope that The Thousand Polish Genomes database will contribute to the worldwide genomic data resources for researchers and clinicians.

genomics↗

bioRxiv2019

Dynamic architecture of the Escherichia coli structural maintenance of chromosomes (SMC) complex, MukBEF

Structural Maintenance of Chromosomes (SMC) complexes use a proteinaceous ring-shaped architecture to organise chromosomes, thereby facilitating chromosome segregation. They utilise cycles of ATP binding and hydrolysis to transport themselves rapidly with respect to DNA, a process requiring protein conformational changes and multiple DNA contacts. We have analysed changes in the architecture of the Escherichia coli SMC complex, MukBEF, as a function of nucleotide binding to MukB and subsequent ATP hydrolysis. This builds upon previous work showing that MukF kleisin directs formation of a MukBEF tripartite ring as a consequence of functional interactions between the C- and N-terminal domains of MukF with the MukB head and neck, respectively (Zawadzka et al., 2018). Using both model truncated substrates and complexes containing full length MukB, we now demonstrate formation of MukBEF dimers of dimers, dependent on MukF dimerization, MukB head-engagement and MukE, which plays an essential role in organizing MukBEF complexes.

biochemistry↗

bioRxiv2017

Asymmetric MukB ATPases are regulated independently by the N- and C-terminal domains of MukF kleisin

The Escherichia coli SMC complex, MukBEF, acts in chromosome segregation. MukBEF shares the distinctive architecture of other SMC complexes, with one prominent difference; unlike other kleisins, MukF forms dimers through its N-terminal domain. We show that a 4-helix bundle adjacent to the MukF dimerization domain interacts functionally with the MukB coiled-coiled neck adjacent to the ATPase head, forming an asymmetric tripartite complex, as in other SMC complexes. Since MukF dimerization is preserved during this interaction, MukF directs the formation of dimer of dimers MukBEF complexes, observed previously in vivo. The MukF N- and C-terminal domains stimulate ATPase independently and additively, consistent with them each targeting only one of the two MukB ATPase active sites in the asymmetric complex. We demonstrate that MukF interaction with the MukB neck turns over during cycles of ATP binding and hydrolysis in vivo and that impairment of this interaction leads to MukBEF release from chromosomes.

biochemistry↗