|
rdf:type |
|
|
lifeskim:mentions |
|
|
pubmed:issue |
7
|
|
pubmed:dateCreated |
2005-7-14
|
|
pubmed:abstractText |
Premature aging syndromes often result from mutations in nuclear proteins involved in the maintenance of genomic integrity. Lamin A is a major component of the nuclear lamina and nuclear skeleton. Truncation in lamin A causes Hutchinson-Gilford progerial syndrome (HGPS), a severe form of early-onset premature aging. Lack of functional Zmpste24, a metalloproteinase responsible for the maturation of prelamin A, also results in progeroid phenotypes in mice and humans. We found that Zmpste24-deficient mouse embryonic fibroblasts (MEFs) show increased DNA damage and chromosome aberrations and are more sensitive to DNA-damaging agents. Bone marrow cells isolated from Zmpste24-/- mice show increased aneuploidy and the mice are more sensitive to DNA-damaging agents. Recruitment of p53 binding protein 1 (53BP1) and Rad51 to sites of DNA lesion is impaired in Zmpste24-/- MEFs and in HGPS fibroblasts, resulting in delayed checkpoint response and defective DNA repair. Wild-type MEFs ectopically expressing unprocessible prelamin A show similar defects in checkpoint response and DNA repair. Our results indicate that unprocessed prelamin A and truncated lamin A act dominant negatively to perturb DNA damage response and repair, resulting in genomic instability which might contribute to laminopathy-based premature aging.
|
|
pubmed:commentsCorrections |
|
|
pubmed:language |
eng
|
|
pubmed:journal |
|
|
pubmed:citationSubset |
IM
|
|
pubmed:chemical |
http://linkedlifedata.com/resource/pubmed/chemical/Chromosomal Proteins, Non-Histone,
http://linkedlifedata.com/resource/pubmed/chemical/DNA,
http://linkedlifedata.com/resource/pubmed/chemical/DNA-Binding Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/H2AX protein, mouse,
http://linkedlifedata.com/resource/pubmed/chemical/Histones,
http://linkedlifedata.com/resource/pubmed/chemical/Intracellular Signaling Peptides...,
http://linkedlifedata.com/resource/pubmed/chemical/Lamin Type A,
http://linkedlifedata.com/resource/pubmed/chemical/Membrane Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/Metalloendopeptidases,
http://linkedlifedata.com/resource/pubmed/chemical/Nuclear Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/Phosphoproteins,
http://linkedlifedata.com/resource/pubmed/chemical/Protein Precursors,
http://linkedlifedata.com/resource/pubmed/chemical/RAD51 protein, human,
http://linkedlifedata.com/resource/pubmed/chemical/Rad51 Recombinase,
http://linkedlifedata.com/resource/pubmed/chemical/Rad51 protein, mouse,
http://linkedlifedata.com/resource/pubmed/chemical/TP53BP1 protein, human,
http://linkedlifedata.com/resource/pubmed/chemical/Trp53bp1 protein, mouse,
http://linkedlifedata.com/resource/pubmed/chemical/Zmpste24 protein, mouse,
http://linkedlifedata.com/resource/pubmed/chemical/prelamin A
|
|
pubmed:status |
MEDLINE
|
|
pubmed:month |
Jul
|
|
pubmed:issn |
1078-8956
|
|
pubmed:author |
pubmed-author:CadiñanosJuanJ,
pubmed-author:CaoYihaiY,
pubmed-author:ChanKui MingKM,
pubmed-author:ChauPui YinPY,
pubmed-author:CheahKathryn S EKS,
pubmed-author:ChenDavid JDJ,
pubmed-author:ChenJunjieJ,
pubmed-author:DengWenW,
pubmed-author:GuanXinyuanX,
pubmed-author:HuangJian-dongJD,
pubmed-author:HutchisonChrisC,
pubmed-author:López-OtínCarlosC,
pubmed-author:LiKai ManKM,
pubmed-author:LiuBaohuaB,
pubmed-author:PeiDuanqingD,
pubmed-author:PendasAlberto MAM,
pubmed-author:TjiaWai MuiWM,
pubmed-author:TryggvasonKarlK,
pubmed-author:TseHung FatHF,
pubmed-author:WangJianmingJ,
pubmed-author:ZhouZhongjunZ
|
|
pubmed:issnType |
Print
|
|
pubmed:volume |
11
|
|
pubmed:owner |
NLM
|
|
pubmed:authorsComplete |
Y
|
|
pubmed:pagination |
780-5
|
|
pubmed:dateRevised |
2011-11-17
|
|
pubmed:meshHeading |
pubmed-meshheading:15980864-Aging, Premature,
pubmed-meshheading:15980864-Animals,
pubmed-meshheading:15980864-Bone Marrow Cells,
pubmed-meshheading:15980864-Cell Aging,
pubmed-meshheading:15980864-Chromosomal Proteins, Non-Histone,
pubmed-meshheading:15980864-Chromosome Aberrations,
pubmed-meshheading:15980864-DNA,
pubmed-meshheading:15980864-DNA Damage,
pubmed-meshheading:15980864-DNA Repair,
pubmed-meshheading:15980864-DNA-Binding Proteins,
pubmed-meshheading:15980864-Fibroblasts,
pubmed-meshheading:15980864-Gamma Rays,
pubmed-meshheading:15980864-Genomic Instability,
pubmed-meshheading:15980864-Histones,
pubmed-meshheading:15980864-Humans,
pubmed-meshheading:15980864-Intracellular Signaling Peptides and Proteins,
pubmed-meshheading:15980864-Lamin Type A,
pubmed-meshheading:15980864-Membrane Proteins,
pubmed-meshheading:15980864-Metalloendopeptidases,
pubmed-meshheading:15980864-Mice,
pubmed-meshheading:15980864-Mice, Mutant Strains,
pubmed-meshheading:15980864-Nuclear Proteins,
pubmed-meshheading:15980864-Phosphoproteins,
pubmed-meshheading:15980864-Protein Precursors,
pubmed-meshheading:15980864-Rad51 Recombinase
|
|
pubmed:year |
2005
|
|
pubmed:articleTitle |
Genomic instability in laminopathy-based premature aging.
|
|
pubmed:affiliation |
Department of Biochemistry, University of Hong Kong, 21 Sassoon Road, Hong Kong.
|
|
pubmed:publicationType |
Journal Article,
Research Support, Non-U.S. Gov't
|
