Linked Life Data

17560275

Source:http://linkedlifedata.com/resource/pubmed/id/17560275

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:dateCreated
2007-6-11
pubmed:abstractText
To mount an optimum immune response, mature B lymphocytes can change the class of expressed antibody from IgM to IgG, IgA, or IgE through a recombination/deletion process termed immunoglobulin heavy chain (IgH) class switch recombination (CSR). CSR requires the activation-induced cytidine deaminase (AID), which has been shown to employ single-stranded DNA as a substrate in vitro. IgH CSR occurs within and requires large, repetitive sequences, termed S regions, which are parts of germ line transcription units (termed "C(H) genes") that are composed of promoters, S regions, and individual IgH constant region exons. CSR requires and is directed by germ line transcription of participating C(H) genes prior to CSR. AID deamination of cytidines in S regions appears to lead to S region double-stranded breaks (DSBs) required to initiate CSR. Joining of two broken S regions to complete CSR exploits the activities of general DNA DSB repair mechanisms. In this chapter, we discuss our current knowledge of the function of S regions, germ line transcription, AID, and DNA repair in CSR. We present a model for CSR in which transcription through S regions provides DNA substrates on which AID can generate DSB-inducing lesions. We also discuss how phosphorylation of AID may mediate interactions with cofactors that facilitate access to transcribed S regions during CSR and transcribed variable regions during the related process of somatic hypermutation (SHM). Finally, in the context of this CSR model, we further discuss current findings that suggest synapsis and joining of S region DSBs during CSR have evolved to exploit general mechanisms that function to join widely separated chromosomal DSBs.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:issn
0065-2776
pubmed:author
pubmed:issnType
Print
pubmed:volume
94
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
157-214
pubmed:dateRevised
2010-11-18
pubmed:meshHeading
pubmed:year
2007
pubmed:articleTitle
Evolution of the immunoglobulin heavy chain class switch recombination mechanism.
pubmed:affiliation
Immunology Program, Memorial Sloan Kettering Cancer Center, New York, New York, USA.
pubmed:publicationType
Journal Article, Review, Research Support, Non-U.S. Gov't, Research Support, N.I.H., Extramural