کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
---|---|---|---|---|
8320545 | 1539390 | 2016 | 21 صفحه PDF | دانلود رایگان |
عنوان انگلیسی مقاله ISI
Disease-associated repeat instability and mismatch repair
ترجمه فارسی عنوان
عدم تداخل تکراری و اصلاح ناسازگاری مرتبط با بیماری
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کلمات کلیدی
MSH6TNRMSHTrinucleotide repeat instabilityFRAXADM1MutS homologmutL HomologPMS2MSH2MLH1MMRMLHpolymerase betaFXSPolδFRDABERNER - DOWNhESC - hescPolβ - PolbaFriedreich’s Ataxia - آتاکسیا فریدریشamyotrophic lateral sclerosis - اسکلروز جانبی آمیوتروفیکTissue-specific - بافت خاصHuntington’s disease - بیماری هانتینگتونError-prone repair - تعمیر خطا خطاnucleotide excision repair - تعمیر مجدد نوکلئوتیدیmismatch repair - تعمیر ناسازگاریbase excision repair - تعمیر پایه پایهtrinucleotide repeat - تکرار تری انوکلئوتیدR-loops - حلقه های RMyotonic dystrophy - دیستروفی میوتونیکfragile X - شکننده XMyotonic dystrophy type 1 - نوع دیستروفی میوتونیک 1
موضوعات مرتبط
علوم زیستی و بیوفناوری
بیوشیمی، ژنتیک و زیست شناسی مولکولی
زیست شیمی
چکیده انگلیسی
Expanded tandem repeat sequences in DNA are associated with at least 40 human genetic neurological, neurodegenerative, and neuromuscular diseases. Repeat expansion can occur during parent-to-offspring transmission, and arise at variable rates in specific tissues throughout the life of an affected individual. Since the ongoing somatic repeat expansions can affect disease age-of-onset, severity, and progression, targeting somatic expansion holds potential as a therapeutic target. Thus, understanding the factors that regulate this mutation is crucial. DNA repair, in particular mismatch repair (MMR), is the major driving force of disease-associated repeat expansions. In contrast to its anti-mutagenic roles, mammalian MMR curiously drives the expansion mutations of disease-associated (CAG)·(CTG) repeats. Recent advances have broadened our knowledge of both the MMR proteins involved in disease repeat expansions, including: MSH2, MSH3, MSH6, MLH1, PMS2, and MLH3, as well as the types of repeats affected by MMR, now including: (CAG)·(CTG), (CGG)·(CCG), and (GAA)·(TTC) repeats. Mutagenic slipped-DNA structures have been detected in patient tissues, and the size of the slip-out and their junction conformation can determine the involvement of MMR. Furthermore, the formation of other unusual DNA and R-loop structures is proposed to play a key role in MMR-mediated instability. A complex correlation is emerging between tissues showing varying amounts of repeat instability and MMR expression levels. Notably, naturally occurring polymorphic variants of DNA repair genes can have dramatic effects upon the levels of repeat instability, which may explain the variation in disease age-of-onset, progression and severity. An increasing grasp of these factors holds prognostic and therapeutic potential.
ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: DNA Repair - Volume 38, February 2016, Pages 117-126
Journal: DNA Repair - Volume 38, February 2016, Pages 117-126
نویسندگان
Monika H.M. Schmidt, Christopher E. Pearson,