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Nuclear DNA

About: Nuclear DNA is a research topic. Over the lifetime, 3933 publications have been published within this topic receiving 185830 citations.


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TL;DR: Evidence of both negative and adaptive (positive) selection acting on the mtDNA and nDNA-encoded genes and the effect of both types of selection on mito-nuclear interacting factors are discussed.
Abstract: Most cell functions are carried out by interacting factors, thus underlying the functional importance of genetic interactions between genes, termed epistasis. Epistasis could be under strong selective pressures especially in conditions where the mutation rate of one of the interacting partners notably differs from the other. Accordingly, the order of magnitude higher mitochondrial DNA (mtDNA) mutation rate as compared to the nuclear DNA (nDNA) of all tested animals, should influence systems involving mitochondrial-nuclear (mito-nuclear) interactions. Such is the case of the energy producing oxidative phosphorylation (OXPHOS) and mitochondrial translational machineries which are comprised of factors encoded by both the mtDNA and the nDNA. Additionally, the mitochondrial RNA transcription and mtDNA replication systems are operated by nDNA-encoded proteins that bind mtDNA regulatory elements. As these systems are central to cell life there is strong selection towards mito-nuclear co-evolution to maintain their function. However, it is unclear whether (A) mito-nuclear co-evolution befalls only to retain mitochondrial functions during evolution or, also, (B) serves as an adaptive tool to adjust for the evolving energetic demands as species’ complexity increases. As the first step to answer these questions we discuss evidence of both negative and adaptive (positive) selection acting on the mtDNA and nDNA-encoded genes and the effect of both types of selection on mito-nuclear interacting factors. Emphasis is given to the crucial role of recurrent ancient (nodal) mutations in such selective events. We apply this point-of-view to the three available types of mito-nuclear co-evolution: protein-protein (within the OXPHOS system), protein-RNA (mainly within the mitochondrial ribosome) and protein DNA (at the mitochondrial replication and transcription machineries).

78 citations

Journal ArticleDOI
TL;DR: In this article, the influence of chromatin structure on DNA double-strand break induction by X radiation was studied in DNA from CHO cells, including nuclei with condensed or relaxed chromatin, and deproteinized DNA in agarose plugs.
Abstract: The influence of chromatin structure on induction of DNA double-strand breaks (DSBs) by X radiation was studied in DNA from CHO cells. Whole cells, nuclei with condensed or relaxed chromatin, and deproteinized DNA in agarose plugs were irradiated and DSB formation was measured as a decrease in the length of DNA by nondenaturing, pulsed-field, agarose gel electrophoresis. The yield of DSBs in deproteinized DNA (2.3 x 10(-10) DSBs Da-1 Gy-1) was observed to be 70 times greater than the yield of DSBs (3.1 x 10(-12) DSBs Da-1 Gy-1) observed in DNA in the intact cell nucleus. Organization of DNA into the basic nucleosome repeat structure and condensation of the chromatin fiber into higher-order structure protected DNA from DSB induction by factors of 8.3 and 4.5, respectively. An additional twofold protection of DNA in fully condensed chromatin occurred in the intact cell nucleus. Since this protection did not appear to involve chromatin structure, we speculate that this additional protection may result from the association of soluble protein and nonprotein sulfhydryls with DNA in the intact cell nucleus. The results are consistent with the organization of nuclear DNA into both basic nucleosome repeat structure and higher-order chromatin structure providing significant protection against DSB induction.

78 citations

Journal ArticleDOI
TL;DR: In this paper, annealing studies were performed on DNA fragments associated with rat and mouse liver interphase nuclear matrix and the metaphase scaffold of Chinese hamster DON cells.
Abstract: Annealing studies were performed on DNA fragments associated with rat and mouse liver interphase nuclear matrix and the metaphase scaffold of Chinese hamster DON cells. Matrix and scaffold bound DNA fragments, reassociated with an excess of total genomic DNA, displayed kinetics virtually identical with total nuclear DNA probes. Moreover, both the extent and kinetics of these hybridizations were independent of the matrix DNA fragment size (less than 350--5000 base pairs) and the method of nuclease digestion used in their preparation (DNase I, micrococcal nuclease or endogenous digestion). The repetitive DNA component of the matrix DNA was examined by reacting discrete sizes of matrix DNA fragments (less than 350--5000 base pairs) from mouse liver with a library of cloned repetitive sequence DNA fragments which included mouse major satellite sequences. Our results demonstrate that short DNA fragments anchored to the nuclear matrix contain these cloned sequences is similar proportion of total nuclear DNA and, when viewed in light of the annealing results, indicate that matrix DNA is not enriched in either repetitive or unique sequences. Furthermore, the matrix DNA fragments appear to contain the entire sequence complexity of the genome. Finally, we hybridized both matrix and total nuclear DNA fragments with cDNA to total nuclear polyadenylated RNA. The kinetics and extent of hybridization indicate that most, if not all, of the actively transcribed DNA sequences are present in similar concentrations. We conclude that in the overall organization of eukaryotic DNA within the nucleus, the repeating domains or loops which have been demonstrated by a number of investigators are not anchored at specific attachment sequences in interphase cells or during mitosis. These findings are discussed with regard to current concepts of eukaryotic DNA loop organization.

78 citations

Journal ArticleDOI
26 Jul 1991-Cell

78 citations

Journal ArticleDOI
TL;DR: Results demonstrated that both, higher initial binding and lack of removal of cisplatin-DNA adducts appear to contribute to the preferential cisPlatin-mtDNA binding observed in CHO cells.
Abstract: Levels of DNA adducts in Chinese hamster ovary (CHO) cells exposed to cis-diamminedichloroplatinum(II) (cisplatin) for 24 h, have been shown to be 4- to 6-fold higher in mitochondrial (mt) DNA as compared to nuclear (n) DNA (Olivero et al., Mutation Res., 346 (1995) 221). The aim of the present study was to understand if the preferential cisplatin binding in mtDNA is partially caused by lack of adduct removal in the mitochondria. Chinese hamster ovary cells were exposed for 6 h to 50 microM cisplatin, followed by incubation for 24 and 48 h in cisplatin-free medium. At the 30-h time point (6 h with cisplatin, 24 h without cisplatin), half of the cells from each plate were harvested and the remainder were cultured and harvested at 54 h (6 h with cisplatin, 48 h without cisplatin). The 30- and 54-h time points are called 'T30' and 'T54', respectively. Cisplatin-DNA adducts were measured in DNA from nuclear and mitochondrial fractions by dissociation-enhanced lanthanide fluoroimmunoassay (DELFIA), a sensitive competitive microtiter-based immunoassay utilizing antiserum elicited against cisplatin-modified DNA. An initial higher level of cisplatin-DNA adducts was observed in mtDNA when compared to nDNA, at T30. In addition, a lack of removal of adducts in mtDNA was demonstrated in cells at T54. Dilution of DNA adducts by DNA replication was documented in pulse-chase experiments that employed [3H]thymidine incorporation. Adduct removal by repair-related mechanisms was considered to comprise the difference between total DNA adduct removal and adduct removal related to DNA replication. The final results demonstrated that both, higher initial binding and lack of removal of cisplatin-DNA adducts appear to contribute to the preferential cisplatin-mtDNA binding observed in CHO cells.

78 citations


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Performance
Metrics
No. of papers in the topic in previous years
YearPapers
202361
202284
202177
202064
201966
201862