کد مقاله کد نشریه سال انتشار مقاله انگلیسی نسخه تمام متن
1981019 1061894 2006 18 صفحه PDF دانلود رایگان
عنوان انگلیسی مقاله ISI
Computational analyses show A-to-G mutations correlate with nascent mRNA hairpins at somatic hypermutation hotspots
موضوعات مرتبط
علوم زیستی و بیوفناوری بیوشیمی، ژنتیک و زیست شناسی مولکولی زیست شیمی
پیش نمایش صفحه اول مقاله
Computational analyses show A-to-G mutations correlate with nascent mRNA hairpins at somatic hypermutation hotspots
چکیده انگلیسی

Activation-induced cytidine deaminase (AID) initiates Phase I somatic hypermutation (SHM) of antibody genes by deaminating deoxy-cytosine to deoxy-uracil (C-to-U). These lesions trigger Phase II, a poorly understood process of error-prone repair targeting A-T pairs by DNA polymerase η (Pol η). Since Pol η is also a reverse transcriptase, Phase II could involve copying off RNA as well as DNA templates. We explore this idea further since in an RNA-based pathway it is conceivable that adenosine-to-inosine (A-to-I) RNA editing causes A-to-G transitions since I like G pairs with C. Adenosine deaminases (ADARs) are known to preferentially edit A nucleotides that are preceded by an A or U (W) in double-stranded RNA substrates. On this assumption and using a theoretical bioinformatics approach we show that a significant and specific correlation (P < 0.002) exists between the frequency of WA-to-WG mutations and the number of mRNA hairpins that could potentially form at the mutation site. This implies roles for both RNA editing and reverse transcription during SHM in vivo and suggests definitive genetic experiments targeting the appropriate ADAR1 isoform (γINF-ADAR1) and/or Ig pre-mRNA templates.

ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: DNA Repair - Volume 5, Issue 11, 8 November 2006, Pages 1346–1363
نویسندگان
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