دورية أكاديمية
Proximity to AGCT sequences dictates MMR-independent versus MMR-dependent mechanisms for AID-induced mutation via UNG2
| العنوان: | Proximity to AGCT sequences dictates MMR-independent versus MMR-dependent mechanisms for AID-induced mutation via UNG2 |
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| المؤلفون: | Thientosapol, ES, Sharbeen, G, Edwin Lau, KK, Bosnjak, D, Durack, T, Stevanovski, I, Weninger, W, Jolly, CJ |
| المصدر: | urn:ISSN:0305-1048 ; urn:ISSN:1362-4962 ; Nucleic Acids Research, 45, 6, 3146-3157 |
| بيانات النشر: | Oxford University Press |
| سنة النشر: | 2017 |
| المجموعة: | UNSW Sydney (The University of New South Wales): UNSWorks |
| مصطلحات موضوعية: | Genetics, Adoptive Transfer, Animals, Base Pairing, Base Sequence, Cytidine Deaminase, DNA Mismatch Repair, DNA Repair, Male, Mice, Inbred C57BL, Mutation, Uracil, Uracil-DNA Glycosidase, anzsrc-for: 05 Environmental Sciences, anzsrc-for: 06 Biological Sciences, anzsrc-for: 08 Information and Computing Sciences |
| الوصف: | AID deaminates C to U in either strand of Ig genes, exclusively producing C:G/G:C to T:A/A:T transition mutations if U is left unrepaired. Error-prone processing by UNG2 or mismatch repair diversifies mutation, predominantly at C:G or A:T base pairs, respectively. Here, we show that transversions at C:G base pairs occur by two distinct processing pathways that are dictated by sequence context. Within and near AGCT mutation hotspots, transversion mutation at C:G was driven by UNG2 without requirement for mismatch repair. Deaminations in AGCT were refractive both to processing by UNG2 and to high-fidelity base excision repair (BER) downstream of UNG2, regardless of mismatch repair activity. We propose that AGCT sequences resist faithful BER because they bind BER-inhibitory protein(s) and/or because hemi-deaminated AGCT motifs innately form a BERresistant DNA structure. Distal to AGCT sequences, transversions at G were largely co-dependent on UNG2 and mismatch repair. We propose that AGCTdistal transversions are produced when apyrimidinic sites are exposed in mismatch excision patches, because completion of mismatch repair would require bypass of these sites. |
| نوع الوثيقة: | article in journal/newspaper |
| وصف الملف: | application/pdf |
| اللغة: | unknown |
| العلاقة: | http://hdl.handle.net/1959.4/unsworks_57335Test; https://unsworks.unsw.edu.au/bitstreams/b146c6ed-fcaf-414c-8cd9-d852ee08860a/downloadTest; https://doi.org/10.1093/nar/gkw1300Test |
| DOI: | 10.1093/nar/gkw1300 |
| الإتاحة: | https://doi.org/10.1093/nar/gkw1300Test http://hdl.handle.net/1959.4/unsworks_57335Test https://unsworks.unsw.edu.au/bitstreams/b146c6ed-fcaf-414c-8cd9-d852ee08860a/downloadTest |
| حقوق: | open access ; https://purl.org/coar/access_right/c_abf2Test ; CC BY-NC ; https://creativecommons.org/licenses/by-nc/4.0Test/ ; free_to_read ; This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by-nc/4.0Test/), which permits non-commercial re-use, distribution, and reproduction in any medium, provided the original work is properly cited. For commercial re-use, please contact journals.permissions@oup.com |
| رقم الانضمام: | edsbas.CABEC1C0 |
| قاعدة البيانات: | BASE |
| DOI: | 10.1093/nar/gkw1300 |
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