Document Detail


Ligase IV syndrome.
MedLine Citation:
PMID:  20687505     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Ligase IV (LIG4) syndrome belongs to the group of hereditary disorders associated with impaired DNA damage response mechanisms. Clinically and morphologically, patients affected with this syndrome are characterized by microcephaly, unusual facial features, growth retardation, developmental delay, skin anomalies and are typically pancytopenic. The disease leads to acute radiosensitivity, immunodeficiency and bone marrow abnormalities. LIG4 syndrome arises from hypomorphic mutations in the LIG4 gene encoding DNA ligase IV; a component of the nonhomologous end-joining machinery, which represents a major mechanism of repair of double strand DNA breaks in mammals. The hypomorphic mutations do not completely abolish but significantly reduce enzyme function. This results in impaired V(D)J recombination, the essential rejoining process in T- and B-cell development, in whose ligase IV plays the key role. As a consequence, patients with LIG4 syndrome frequently develop multiple immune abnormalities, clinically overlapping with severe combined immunodeficiency syndrome.
Authors:
Dimitry A Chistiakov
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Publication Detail:
Type:  Journal Article; Review    
Journal Detail:
Title:  Advances in experimental medicine and biology     Volume:  685     ISSN:  0065-2598     ISO Abbreviation:  Adv. Exp. Med. Biol.     Publication Date:  2010  
Date Detail:
Created Date:  2010-08-06     Completed Date:  2010-08-20     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  0121103     Medline TA:  Adv Exp Med Biol     Country:  United States    
Other Details:
Languages:  eng     Pagination:  175-85     Citation Subset:  IM    
Affiliation:
Department of Molecular Diagnostics, National Research Center GosNIIGenetika, 1st Dorozhny Proezd 1, 117545 Moscow, Russia. dimitry.chistiakov@lycos.com
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MeSH Terms
Descriptor/Qualifier:
Animals
B-Lymphocytes / enzymology
Bone Marrow Diseases* / enzymology,  genetics
DNA Breaks, Double-Stranded
DNA Ligases* / genetics,  metabolism
DNA Repair-Deficiency Disorders* / enzymology,  genetics
Humans
Mutation*
Radiation Tolerance / genetics*
Recombination, Genetic / genetics
Skin Diseases, Genetic* / enzymology,  genetics
Syndrome
T-Lymphocytes / enzymology
Chemical
Reg. No./Substance:
EC 6.5.1.-/DNA Ligases; EC 6.5.1.1/DNA ligase (ATP)

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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