Linked Life Data

11841555

Source:http://linkedlifedata.com/resource/pubmed/id/11841555

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
2
pubmed:dateCreated
2002-2-13
pubmed:abstractText
Of the eight human genes implicated in xeroderma pigmentosum, defects in XPG produce some of the most clinically diverse symptoms. These range from mild freckling to severe skeletal and neurologic abnormalities characteristic of Cockayne syndrome. Mildly affected xeroderma pigmentosum group G patients have diminished XPG endonuclease activity in nucleotide excision repair, whereas severely affected xeroderma pigmentosum group G/Cockayne syndrome patients produce truncated XPG proteins that are unable to function in either nucleotide excision repair or the transcription-coupled repair of oxidative lesions. The first two xeroderma pigmentosum group G patients, XP2BI and XP3BR, were reported before the relationship between xeroderma pigmentosum group G and Cockayne syndrome was appreciated. Here we provide evidence that both patients produce truncated proteins from one XPG allele. From the second allele, XP2BI generates full-length XPG of 1186 amino acids containing a single L858P substitution that has reduced stability and greatly impaired endonuclease activity. In XP3BR, a single base deletion and alternative splicing at a rare noncanonical AT-AC intron produces a 1185 amino acid protein containing 44 internal non-XPG residues. This protein is stably expressed but it also has greatly impaired endonuclease activity. These four XPG products can thus account for the severe ultraviolet sensitivity of XP2BI and XP3BR fibroblasts. These cells, unlike those from xeroderma pigmentosum group G/Cockayne syndrome patients, are capable of limited transcription-coupled repair of oxidative lesions. Our results suggest that the L858P protein in XP2BI and the almost full-length XPG protein in XP3BR are responsible for this activity and for the absence of severe early onset Cockayne syndrome symptoms in these patients.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Feb
pubmed:issn
0022-202X
pubmed:author
pubmed:issnType
Print
pubmed:volume
118
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
344-51
pubmed:dateRevised
2006-11-15
pubmed:meshHeading
pubmed:year
2002
pubmed:articleTitle
The founding members of xeroderma pigmentosum group G produce XPG protein with severely impaired endonuclease activity.
pubmed:affiliation
Department of Genetics and Microbiology, Centre Médical Universitaire (CMU), Geneva, Switzerland.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't