Activities of human exonuclease 1 that promote cleavage of transcribed immunoglobulin switch regions
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 d...
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| Veröffentlicht in: | Proceedings of the National Academy of Sciences - PNAS 2008-10, Vol.105 (43), p.16508-16512 |
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| container_title | Proceedings of the National Academy of Sciences - PNAS |
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| creator | Vallur, Aarthy C Maizels, Nancy |
| description | 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. |
| doi_str_mv | 10.1073/pnas.0805327105 |
| format | Article |
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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. 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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. 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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.</abstract><cop>United States</cop><pub>National Academy of Sciences</pub><pmid>18940926</pmid><doi>10.1073/pnas.0805327105</doi><tpages>5</tpages><oa>free_for_read</oa></addata></record> |
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| subjects | AIDS Animals B lymphocytes Biological Sciences Cytidine Deaminase - metabolism Deoxyribonucleic acid DNA DNA mismatch repair DNA Repair Enzymes - metabolism DNA Repair Enzymes - physiology Enzyme substrates Enzymes Eukaryotes Exodeoxyribonucleases - metabolism Exodeoxyribonucleases - physiology Humans Hybridity Hydrolysis Immunoglobulin Class Switching - genetics Immunoglobulin Switch Region - genetics Immunoglobulins Immunology Mice Mice, Knockout Plasmids Promoter regions RNA Transcription, Genetic |
| title | Activities of human exonuclease 1 that promote cleavage of transcribed immunoglobulin switch regions |
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