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@misc{1354013,
author = {Paleček, Jan and Vondrová, Lucie and Adamus, Marek and Zábrady, Kateřina and Jurčišinová, Lenka and Bozděchová, Lucie and Crabben, Saskia N van der and Hennus, Marije P and McGregor, Grant and Ritter, Deborah I and Lehmann, Alan R and Oliver, Antony William and Plon, Sharon E and Murray, Johanne M and Haaften, Gijs van},
booktitle = {7th DNA Repair Workshop},
language = {eng},
title = {Evolution, functions and pathogenesis of the Nse3 (KITE) subunit of the SMC5/6 complex},
year = {2016}
}
TY - SLIDE
ID - 1354013
AU - Paleček, Jan - Vondrová, Lucie - Adamus, Marek - Zábrady, Kateřina - Jurčišinová, Lenka - Bozděchová, Lucie - Crabben, Saskia N van der - Hennus, Marije P - McGregor, Grant - Ritter, Deborah I - Lehmann, Alan R - Oliver, Antony William - Plon, Sharon E - Murray, Johanne M - Haaften, Gijs van
PY - 2016
TI - Evolution, functions and pathogenesis of the Nse3 (KITE) subunit of the SMC5/6 complex
N2 - The SMC (structure maintenance of chromosome) complexes are conserved from bacteria to humans. They are key components of higher-order chromatin structures and play important roles in genome stability. The SMC5/6 complex is involved in the homologous recombination-based DNA repair, in replication fork stability and processing, and in cohesin regulation. Eight subunits compose the SMC5/6 complex and contribute to its functions and dynamics. Recently, we discovered several important features of the Nse3 subunit: its role in structural organization of the SMC5/6 complex, its DNA-binding ability, its evolution from bacteria to novel mammalian protein family. In addition, we described new chromosome breakage syndrome associated with Nse3 mutations. We will present our in depth analysis of Nse3 interactions with other Nse subunits of the SMC5/6 complex and their role in structural organization of the SMC5/6 complex. Via these interactions, Nse3 forms Nse1/Nse3/Nse4 sub-complex which (in addition) binds to DNA and assists in loading of SMC5/6 to chromatin. In vivo studies of Schizosaccharomyces pombe nse3 mutants suggest Nse3 essential role in chromatin protection and organization (yeast cells exhibit chromatin aberrations and hypersensitivity to DNA damaging agents). In addition to yeast studies, we will present the new chromosome breakage syndrome associated with severe lung disease in early childhood. Four children from two unrelated kindreds died during infancy of severe pulmonary disease following viral pneumonia with evidence of combined T- and B-cell immunodeficiency. Whole exome sequencing revealed biallelic missense mutations in NSE3, which disrupt NSE3 interactions within the SMC5/6 complex, leading to destabilization of the complex. Patient cells showed chromosome rearrangements, micronuclei, sensitivity to replication stress and DNA damage, and defective homologous recombination.
ER -
PALEČEK, Jan, Lucie VONDROVÁ, Marek ADAMUS, Kateřina ZÁBRADY, Lenka JURČIŠINOVÁ, Lucie BOZDĚCHOVÁ, Saskia N van der CRABBEN, Marije P HENNUS, Grant MCGREGOR, Deborah I RITTER, Alan R LEHMANN, Antony William OLIVER, Sharon E PLON, Johanne M MURRAY and Gijs van HAAFTEN. Evolution, functions and pathogenesis of the Nse3 (KITE) subunit of the SMC5/6 complex. In \textit{7th DNA Repair Workshop}. 2016.
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