Linked Life Data

18273020

Source:http://linkedlifedata.com/resource/pubmed/id/18273020

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
7180
pubmed:dateCreated
2008-2-14
pubmed:abstractText
Somatic hypermutation introduces point mutations into immunoglobulin genes in germinal centre B cells during an immune response. The reaction is initiated by cytosine deamination by the activation-induced deaminase (AID) and completed by error-prone processing of the resulting uracils by mismatch and base excision repair factors. Somatic hypermutation represents a threat to genome integrity and it is not known how the B cell genome is protected from the mutagenic effects of somatic hypermutation nor how often these protective mechanisms fail. Here we show, by extensive sequencing of murine B cell genes, that the genome is protected by two distinct mechanisms: selective targeting of AID and gene-specific, high-fidelity repair of AID-generated uracils. Numerous genes linked to B cell tumorigenesis, including Myc, Pim1, Pax5, Ocab (also called Pou2af1), H2afx, Rhoh and Ebf1, are deaminated by AID but escape acquisition of most mutations through the combined action of mismatch and base excision repair. However, approximately 25% of expressed genes analysed were not fully protected by either mechanism and accumulated mutations in germinal centre B cells. Our results demonstrate that AID acts broadly on the genome, with the ultimate distribution of mutations determined by a balance between high-fidelity and error-prone DNA repair.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Feb
pubmed:issn
1476-4687
pubmed:author
pubmed:issnType
Electronic
pubmed:day
14
pubmed:volume
451
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
841-5
pubmed:meshHeading
pubmed:year
2008
pubmed:articleTitle
Two levels of protection for the B cell genome during somatic hypermutation.
pubmed:affiliation
Department of Immunobiology, Yale University School of Medicine, New Haven, Connecticut 06510, USA.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't