Destabilized SMC5/6 complex leads to chromosome breakage
syndrome with severe lung disease

J 2016

Destabilized SMC5/6 complex leads to chromosome breakage syndrome with severe lung disease

VAN DER CRABBEN, Saskia, Marije HENNUS, Grant MCGREGOR, Deborah RITTER, Sandesh NAGAMANI et. al.

Basic information

Original name

Destabilized SMC5/6 complex leads to chromosome breakage syndrome with severe lung disease

Authors

VAN DER CRABBEN, Saskia (528 Netherlands), Marije HENNUS (528 Netherlands), Grant MCGREGOR (826 United Kingdom of Great Britain and Northern Ireland), Deborah RITTER (840 United States of America), Sandesh NAGAMANI (840 United States of America), Owen WELLS (826 United Kingdom of Great Britain and Northern Ireland), Magdalena HARAKALOVA (203 Czech Republic), Ivan CHINN (840 United States of America), Aaron ALT (826 United Kingdom of Great Britain and Northern Ireland), Lucie VONDROVÁ (203 Czech Republic, belonging to the institution), Ron HOCHSTENBACH (528 Netherlands), Joris VAN MONTFRANS (528 Netherlands), Suzanne TERHEGGEN-LAGRO (840 United States of America), Stef VAN LIESHOUT (528 Netherlands), Markus VAN ROOSMALEN (528 Netherlands), Ivo RENKENS (528 Netherlands), Karen DURAN (528 Netherlands), Isaac NIJMAN (528 Netherlands), Wigard KLOOSTERMAN (528 Netherlands), Eric HENNEKAM (528 Netherlands), Jordan ORANGE (840 United States of America), Peter VAN HASSELT (528 Netherlands), David WHEELER (840 United States of America), Jan PALEČEK (203 Czech Republic, guarantor, belonging to the institution), Alan LEHMANN (826 United Kingdom of Great Britain and Northern Ireland), Antony William OLIVER (826 United Kingdom of Great Britain and Northern Ireland), Laurence PEARL (826 United Kingdom of Great Britain and Northern Ireland), Sharon PLON (840 United States of America), Johanne MURRAY (826 United Kingdom of Great Britain and Northern Ireland) and Gijs VAN HAAFTEN (528 Netherlands)

Edition

Journal of Clinical Investigation, Ann Arbor, AMER SOC CLINICAL INVESTIGATION INC, 2016, 0021-9738

Other information

Language

English

Type of outcome

Článek v odborném periodiku

Field of Study

Genetics and molecular biology

Country of publisher

United States of America

Confidentiality degree

není předmětem státního či obchodního tajemství

References:

URL

Impact factor

Impact factor: 12.784

RIV identification code

RIV/00216224:14740/16:00088165

Organization unit

Central European Institute of Technology

DOI

http://dx.doi.org/10.1172/JCI82890

UT WoS

000381943000013

Keywords in English

STALLED REPLICATION FORKS; DOUBLE-STRAND BREAKS; HUMAN CELL STRAINS; DNA-REPAIR; HOMOLOGOUS RECOMBINATION; ATAXIA-TELANGIECTASIA; LIGASE ACTIVITY; GENE; PROTEINS; IDENTIFICATION

Abstract

V originále

The structural maintenance of chromosomes (SMC) family of proteins supports mitotic proliferation, meiosis, and DNA repair to control genomic stability. Impairments in chromosome maintenance are linked to rare chromosome breakage disorders. Here, we have identified a chromosome breakage syndrome associated with severe lung disease in early childhood. Four children from two unrelated kindreds died of severe pulmonary disease during infancy following viral pneumonia with evidence of combined T and B cell immunodeficiency. Whole exome sequencing revealed biallelic missense mutations in the NSMCE3 (also known as NDNL2) gene, which encodes a subunit of the SMC5/6 complex that is essential for DNA damage response and chromosome segregation. The NSMCE3 mutations disrupted 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. This work associates missense mutations in NSMCE3 with an autosomal recessive chromosome breakage syndrome that leads to defective T and B cell function and acute respiratory distress syndrome in early childhood.

Links

GA13-00774S, research and development project

Name: Úloha proteinů Nse, podjednotek komplexu SMC5/6, v procesech stabilizujících pozastavené replikační vidlice

Investor: Czech Science Foundation

LQ1601, research and development project

Name: CEITEC 2020 (Acronym: CEITEC2020)

Investor: Ministry of Education, Youth and Sports of the CR

Citovat

VAN DER CRABBEN, Saskia, Marije HENNUS, Grant MCGREGOR, Deborah RITTER, Sandesh NAGAMANI, Owen WELLS, Magdalena HARAKALOVA, Ivan CHINN, Aaron ALT, Lucie VONDROVÁ, Ron HOCHSTENBACH, Joris VAN MONTFRANS, Suzanne TERHEGGEN-LAGRO, Stef VAN LIESHOUT, Markus VAN ROOSMALEN, Ivo RENKENS, Karen DURAN, Isaac NIJMAN, Wigard KLOOSTERMAN, Eric HENNEKAM, Jordan ORANGE, Peter VAN HASSELT, David WHEELER, Jan PALEČEK, Alan LEHMANN, Antony William OLIVER, Laurence PEARL, Sharon PLON, Johanne MURRAY and Gijs VAN HAAFTEN. Destabilized SMC5/6 complex leads to chromosome breakage syndrome with severe lung disease. Journal of Clinical Investigation. Ann Arbor: AMER SOC CLINICAL INVESTIGATION INC, 2016, vol. 126, No 8, p. 2881-2892. ISSN 0021-9738. Available from: https://dx.doi.org/10.1172/JCI82890.

@article{1354532,
   author = {van der Crabben, Saskia and Hennus, Marije and McGregor, Grant and Ritter, Deborah and Nagamani, Sandesh and Wells, Owen and Harakalova, Magdalena and Chinn, Ivan and Alt, Aaron and Vondrová, Lucie and Hochstenbach, Ron and van Montfrans, Joris and TerheggenandLagro, Suzanne and van Lieshout, Stef and van Roosmalen, Markus and Renkens, Ivo and Duran, Karen and Nijman, Isaac and Kloosterman, Wigard and Hennekam, Eric and Orange, Jordan and van Hasselt, Peter and Wheeler, David and Paleček, Jan and Lehmann, Alan and Oliver, Antony William and Pearl, Laurence and Plon, Sharon and Murray, Johanne and van Haaften, Gijs},
   article_location = {Ann Arbor},
   article_number = {8},
   doi = {http://dx.doi.org/10.1172/JCI82890},
   keywords = {STALLED REPLICATION FORKS; DOUBLE-STRAND BREAKS; HUMAN CELL STRAINS; DNA-REPAIR; HOMOLOGOUS RECOMBINATION; ATAXIA-TELANGIECTASIA; LIGASE ACTIVITY; GENE; PROTEINS; IDENTIFICATION},
   language = {eng},
   issn = {0021-9738},
   journal = {Journal of Clinical Investigation},
   title = {Destabilized SMC5/6 complex leads to chromosome breakage syndrome with severe lung disease},
   url = {https://www.jci.org/articles/view/82890},
   volume = {126},
   year = {2016}
}

TY  - JOUR
ID  - 1354532
AU  - van der Crabben, Saskia - Hennus, Marije - McGregor, Grant - Ritter, Deborah - Nagamani, Sandesh - Wells, Owen - Harakalova, Magdalena - Chinn, Ivan - Alt, Aaron - Vondrová, Lucie - Hochstenbach, Ron - van Montfrans, Joris - Terheggen-Lagro, Suzanne - van Lieshout, Stef - van Roosmalen, Markus - Renkens, Ivo - Duran, Karen - Nijman, Isaac - Kloosterman, Wigard - Hennekam, Eric - Orange, Jordan - van Hasselt, Peter - Wheeler, David - Paleček, Jan - Lehmann, Alan - Oliver, Antony William - Pearl, Laurence - Plon, Sharon - Murray, Johanne - van Haaften, Gijs
PY  - 2016
TI  - Destabilized SMC5/6 complex leads to chromosome breakage syndrome with severe lung disease
JF  - Journal of Clinical Investigation
VL  - 126
IS  - 8
SP  - 2881-2892
EP  - 2881-2892
PB  - AMER SOC CLINICAL INVESTIGATION INC
SN  - 00219738
KW  - STALLED REPLICATION FORKS
KW  - DOUBLE-STRAND BREAKS
KW  - HUMAN CELL STRAINS
KW  - DNA-REPAIR
KW  - HOMOLOGOUS RECOMBINATION
KW  - ATAXIA-TELANGIECTASIA
KW  - LIGASE ACTIVITY
KW  - GENE
KW  - PROTEINS
KW  - IDENTIFICATION
UR  - https://www.jci.org/articles/view/82890
L2  - https://www.jci.org/articles/view/82890
N2  - The structural maintenance of chromosomes (SMC) family of proteins supports mitotic proliferation, meiosis, and DNA repair to control genomic stability. Impairments in chromosome maintenance are linked to rare chromosome breakage disorders. Here, we have identified a chromosome breakage syndrome associated with severe lung disease in early childhood. Four children from two unrelated kindreds died of severe pulmonary disease during infancy following viral pneumonia with evidence of combined T and B cell immunodeficiency. Whole exome sequencing revealed biallelic missense mutations in the NSMCE3 (also known as NDNL2) gene, which encodes a subunit of the SMC5/6 complex that is essential for DNA damage response and chromosome segregation. The NSMCE3 mutations disrupted 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. This work associates missense mutations in NSMCE3 with an autosomal recessive chromosome breakage syndrome that leads to defective T and B cell function and acute respiratory distress syndrome in early childhood.
ER  -

VAN DER CRABBEN, Saskia, Marije HENNUS, Grant MCGREGOR, Deborah RITTER, Sandesh NAGAMANI, Owen WELLS, Magdalena HARAKALOVA, Ivan CHINN, Aaron ALT, Lucie VONDROVÁ, Ron HOCHSTENBACH, Joris VAN MONTFRANS, Suzanne TERHEGGEN-LAGRO, Stef VAN LIESHOUT, Markus VAN ROOSMALEN, Ivo RENKENS, Karen DURAN, Isaac NIJMAN, Wigard KLOOSTERMAN, Eric HENNEKAM, Jordan ORANGE, Peter VAN HASSELT, David WHEELER, Jan PALEČEK, Alan LEHMANN, Antony William OLIVER, Laurence PEARL, Sharon PLON, Johanne MURRAY and Gijs VAN HAAFTEN. Destabilized SMC5/6 complex leads to chromosome breakage syndrome with severe lung disease. \textit{Journal of Clinical Investigation}. Ann Arbor: AMER SOC CLINICAL INVESTIGATION INC, 2016, vol.~126, No~8, p.~2881-2892. ISSN~0021-9738. Available from: https://dx.doi.org/10.1172/JCI82890.

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