Activities of human exonuclease 1 that promote cleavage of transcribed immunoglobulin switch regions.
|Title||Activities of human exonuclease 1 that promote cleavage of transcribed immunoglobulin switch regions.|
|Publication Type||Journal Article|
|Year of Publication||2008|
|Authors||Vallur AC, Maizels N|
|Journal||Proceedings of the National Academy of Sciences of the United States of America|
|Date Published||2008 Oct 28|
|Keywords||Animals, Cytidine Deaminase, DNA Repair Enzymes, Exodeoxyribonucleases, Humans, Hydrolysis, Immunoglobulin Class Switching, Immunoglobulin Switch Region, Mice, Mice, Knockout, Transcription, Genetic|
Eukaryotic exonuclease 1 functions in replication, recombination, mismatch repair, telomere maintenance, immunoglobulin (Ig) gene class switch recombination, and somatic hypermutation. The enzyme has 5'-3' exonuclease, flap endonuclease, and weak RNaseH activity in vitro, but it has been difficult to reconcile these activities with its diverse biological functions. We report robust cleavage by human exonuclease 1 of transcribed G-rich DNA sequences with potential to form G loops and G4 DNA. Predicted Ig switch recombination intermediates are substrates for both exonucleolytic and 5' flap endonucleolytic cleavage. Excision is nick-dependent and structure-dependent. These results lead to a model for exonuclease 1 function in class switch recombination in which cleavage at activation-induced deaminase (AID)-initiated nicks produces gaps that become substrates for further attack by AID and subsequent repair.
|Alternate Journal||Proc. Natl. Acad. Sci. U.S.A.|