The unusual structures of the hot-regions flanking large-scale deletions in human mitochondrial DNA.
نویسندگان
چکیده
Large-scale deletions of mitochondrial DNA (mtDNA) are common events that have been found to occur in human ageing and in patients with mitochondrial myopathies. The mechanisms by which these deletions occur remain unclear, but several mechanisms have been proposed, such as slipped-mispairing, illegitimate recombination, and oxidative reactions elicited by free radicals. In addition, the DNA topological stress and local DNA structures have been suggested as the important factors in eliciting the recombinational events. Upon examination of 128 breakpoints of human mtDNA deletions that have been published in the past 8 years, we found that these large-scale deletions often occur at some 'hot-regions'. We thus hypothesized that there exist unusual structures in these regions of human mtDNA that are important for eliciting the deletions. To test this hypothesis, we used PCR techniques to amplify the sequences of the so-called hot-regions and analysed the PCR products by two-dimensional gel electrophoresis. We found that the sequences of nucleotide position (np) 5221-5988, np 6928-7493, np 7901-8732 and np 15327-16228 exhibited retarded mobilities like bent DNA structures; np 5989-6750, np 13282-13653 and np 13282-14850 showed increased mobilities like anti-bent DNA structures. Moreover, except for the sequences of np 1175-1766 found in 12 S and 16 S rRNA genes exhibiting abnormal mobility like bent DNA structures, we did not observe significant mobility abnormalities in the np 499-5545 region where deletions rarely occurred. We thus conclude that these hot-regions assume some kinds of unusual DNA structures, which may render these regions more sensitive to the attack of free radicals or serve as recognition motifs for certain recombination machinery that is involved in the large-scale deletions of human mtDNA.
منابع مشابه
Role of Mitochondria in Ataxia-Telangiectasia: Investigation of Mitochondrial Deletions and Haplogroups
Ataxia-Telangiectasia (AT) is a rare human neurodegenerative autosomal recessive multisystem disease that is characterized by a wide range of features including, progressive cerebellar ataxia with onset during infancy, occulocutaneous telangiectasia, susceptibility to neoplasia, occulomotor disturbances, chromosomal instability and growth and developmental abnormalities. Mitochondrial DNA (mtDN...
متن کاملInvestigation of Polymorphisms in Non-Coding Region of Human Mitochondrial DNA in 31 Iranian Hypertrophic Cardiomyopathy (HCM) Patients
The D-loop region is a hot spot for mitochondrial DNA (mtDNA) alterations, containing two hypervariable segments, HVS-I and HVS-II. In order to identify polymorphic sites and potential genetic background accounting for Hypertrophic CardioMyopathy (HCM) disease, the complete non-coding region of mtDNA from 31 unrelated HCM patients and 45 normal controls were sequenced. The sequences were aligne...
متن کاملشناسایی یک حذف بزرگ در DNA میتوکندریایی بیماران ایرانی مبتلا به آریتمی قلبی
Introduction: Long QT Syndrome is one of the arrhythmic disorders of the heart that causes sudden cardiac death in patients. Most of the investigations have focused on nuclear genome for finding genetic defects in these disorders, but some of the cases with LQTS cannot be explained by mutations of identified genes. It prompted the authors to focus on the mitochondrial DNA and monitor rearrangem...
متن کاملRecombination via flanking direct repeats is a major cause of large-scale deletions of human mitochondrial DNA.
Large-scale deletions of mitochondrial DNA (mtDNA) have been described in patients with progressive external ophthalmoplegia (PEO) and ragged red fibers. We have determined the exact deletion breakpoint in 28 cases with PEO, including 12 patients already shown to harbor an identical deletion; the other patients had 16 different deletions. The deletions fell into two classes. In Class I (9 delet...
متن کاملذخیره در منابع من
با ذخیره ی این منبع در منابع من، دسترسی به آن را برای استفاده های بعدی آسان تر کنید
برای دانلود متن کامل این مقاله و بیش از 32 میلیون مقاله دیگر ابتدا ثبت نام کنید
ثبت ناماگر عضو سایت هستید لطفا وارد حساب کاربری خود شوید
ورودعنوان ژورنال:
- The Biochemical journal
دوره 318 ( Pt 3) شماره
صفحات -
تاریخ انتشار 1996