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11.
The high‐fidelity replicative DNA polymerases, Pol ε and Pol δ, are generally thought to be poorly equipped to replicate damaged DNA. Direct and complete replication of a damaged template therefore typically requires the activity of low‐fidelity translesion synthesis (TLS) polymerases. Here we show that a yeast replisome, reconstituted with purified proteins, is inherently tolerant of the common oxidative lesion thymine glycol (Tg). Surprisingly, leading‐strand Tg was bypassed efficiently in the presence and absence of the TLS machinery. Our data reveal that following helicase–polymerase uncoupling a switch from Pol ε, the canonical leading‐strand replicase, to the lagging‐strand replicase Pol δ, facilitates rapid, efficient and error‐free lesion bypass at physiological nucleotide levels. This replicase switch mechanism also promotes bypass of the unrelated oxidative lesion, 8‐oxoguanine. We propose that replicase switching may promote continued leading‐strand synthesis whenever the replisome encounters leading‐strand damage that is bypassed more efficiently by Pol δ than by Pol ε. 相似文献
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13.
In 1991, treatment with low dose intramuscular desferrioxamine (DFO), a trivalent chelator that can remove excessive iron and/or aluminum from the body, was reported to slow the progression of Alzheimer's disease (AD) by a factor of two. Twenty years later this promising trial has not been followed up and why this treatment worked still is not clear. In this critical interdisciplinary review, we provide an overview of the complexities of AD and involvement of metal ions, and revisit the neglected DFO trial. We discuss research done by us and others that is helping to explain involvement of metal ion catalyzed production of reactive oxygen species in the pathogenesis of AD, and emerging strategies for inhibition of metal-ion toxicity. Highlighted are insights to be considered in the quests to prevent potentially toxic effects of aluminum toxicity and prevention and intervention in AD. 相似文献
14.
Parasites exert a selection pressure on their hosts and are accountable for driving diversity within gene families and immune
gene polymorphisms in a host population. The overwhelming response of regulatory T cells during infectious challenges directs
the host immune system to lose the ability to mount parasite specific T cell responses. The underlying idea of this study
is that regulatory single nucleotide polymorphism (SNPs) can cause significant changes in gene expression in functional immune
genes. We identified and investigated regulatory SNPs in the promoter region of the FOXP3 gene in a group of Gabonese individuals exposed to a variety of parasitic infections. We identified two novel and one promoter
variants in 40 individual subjects. We further validated these promoter variants for their allelic gene expression using transient
transfection assays. Two promoter variants, −794 (C/G) and the other variant −734/−540 (C/T) revealed a significant higher
expression of the reporter gene at basal level in comparison to the major allele. The identification of SNPs that modify function
in the promoter regions could provide a basis for studying parasite susceptibility in association studies. 相似文献
15.
Cytokine-inducible SRC homology 2 domain protein (CISH) is a suppressor of cytokine signaling that controls interleukin-2
signaling pathway. We investigated the single nucleotide polymorphism (SNP) -292A>T in 473 Vietnamese hepatitis B virus (HBV)
carriers and 416 healthy controls. CISH variants at -292A>T were associated to HBV infection (Allelic: OR, 1.22 95% CI, 1–1.49; P = 0.04; Recessive: OR, 1.69 95% CI 1.23–2.54; P = 0.007). A gene dose effect for the risk allele -292T was observed (P = 0.04). The level of interleukin 2 and liver enzymes such as alanine transaminase, aspartate transaminase, total bilirubin,
and direct bilirubin were not associated to CISH polymorphism at position -292A>T This study associated the vital role of CISH SNP -292A>T variant to hepatitis B virus infection in a Vietnamese population. 相似文献
16.
Zea ribosomal repeat evolution and substitution patterns 总被引:2,自引:1,他引:1
Zea and Tripsacum nuclear ribosomal internal transcribed spacer (ITS)
sequences were used to evaluate patterns of concerted evolution, rates of
substitutions, patterns of methylation-induced deamination, and structural
constraints of the ITS. ITS pseudogenes were identified by their
phylogenetic position, differences in nucleotide composition, extensive
deamination at ancestral methylation sites, and substitutions resulting in
low-stability secondary RNA structures. Selection was important in shaping
the kinds of polymorphisms and substitutions observed in the ITS. ITS
substitution rates were significantly different among the Zea taxa.
Deamination of cytosines at methylation sites was a potent mutation source,
but selection appeared to maintain high methylation site density throughout
the ribosomal repeat except for the gene promoter. Nucleotide divergence
statistics identified selectively constrained regions at the 5' ends of the
ITS1 and ITS2.
相似文献
17.
Loss of phylogenetic information in chorion gene families of Bombyx mori gene conversion 总被引:1,自引:0,他引:1
Regier JC; Weigmann BM; Leclerc RF; Friedlander TP 《Molecular biology and evolution》1994,11(1):72-87
The silkmoth chorion has provided a stimulating model for the study of
evolution and developmental regulation of gene families. Previous attempts
at inferring relationships among chorion sequences have been based on
pairwise comparisons of overall similarity, a potentially problematic
approach. To remedy this, we identified the alignable regions of low
sequence variability and then analyzed this restricted database by
parsimony and neighbor-joining methods. At the deepest level, the chorion
sequence tree is split into two branches, called "alpha" and "beta." Within
each branch, early- and late-expressing genes each constitute monophyletic
groups, while the situation with middle-expressing genes remains uncertain.
The HcB gene family appears to be the most basal beta-branch group, but
this conclusion is qualified because the effect of gene conversion on
branching order is unknown. Previous studies by Eickbush and colleagues
have strongly suggested that ErA, HcA, and HcB families undergo gene
conversion within a gene family, whereas the ErB family does not. The
occurrence of conversion correlates with a particular tree structure;
namely, branch lengths are much greater at the base of the family than at
higher internodes and terminal branches. These observations raise the
possibility that chorion gene families are defined by gene conversion
events (reticulate evolution) rather than by descent with modification
(synapomorphy).
相似文献
18.
Implications of mucilage on pressure bomb measurements and water lifting in trees rooting in high-salinity water 总被引:2,自引:0,他引:2
19.
Zimmermann D Westhoff M Zimmermann G Gessner P Gessner A Wegner LH Rokitta M Ache P Schneider H Vásquez JA Kruck W Shirley S Jakob P Hedrich R Bentrup FW Bamberg E Zimmermann U 《Protoplasma》2007,232(1-2):11-34
The water supply to leaves of 25 to 60 m tall trees (including high-salinity-tolerant ones) was studied. The filling status of the xylem vessels was determined by xylem sap extraction (using jet-discharge, gravity-discharge, and centrifugation) and by (1)H nuclear magnetic resonance imaging of wood pieces. Simultaneously, pressure bomb experiments were performed along the entire trunk of the trees up to a height of 57 m. Clear-cut evidence was found that the balancing pressure (P(b)) values of leafy twigs were dictated by the ambient relative humidity rather than by height. Refilling of xylem vessels of apical leaves (branches) obviously mainly occurred via moisture uptake from the atmosphere. These findings could be traced back to the hydration and rehydration of mucilage layers on the leaf surfaces and/or of epistomatal mucilage plugs. Xylem vessels also contained mucilage. Mucilage formation was apparently enforced by water stress. The observed mucilage-based foliar water uptake and humidity dependency of the P(b) values are at variance with the cohesion-tension theory and with the hypothesis that P(b) measurements yield information about the relationships between xylem pressure gradients and height. 相似文献
20.
The objective of the study was to examine salivary biomarker response to fluid consumption in exercising athletes. Exercise induces stress on the body and salivary alpha amylase (sAA) and salivary cortisol are useful biomarkers for activity in the sympathoadrenal medullary system and the hypothalamic pituitary adrenal axis which are involved in the stress response. Fifteen college students were given 150 ml and 500 ml of water on different days and blinded to fluid condition. The exercise protocol was identical for both fluid conditions using absolute exercise intensities ranging from moderate to high. Saliva was collected prior to exercise, post moderate and post high intensities and analyzed by Salimetrics assays. Exercise was significant for sAA with values different between pre-exercise (85 ± 10 U · ml−1) and high intensity (284 ± 30 U · ml−1) as well as between moderate intensity (204 ± 32 U · ml−1) and high intensity. There was no difference in sAA values between fluid conditions at either intensity. Exercise intensity and fluid condition were each significant for cortisol. Cortisol values were different between pre-exercise (0.30 ± 0.03 ug · dL−1) and high intensity (0.45 ± 0.05 ug · dL−1) as well as between moderate intensity (0.33 ± 0.04 ug · dL−1) and high intensity. Moderate exercise intensity cortisol was lower in the 500 ml condition (0.33 ± 0.03 ug · dL−1) compared with the 150 ml condition (0.38 ± 0.03 ug · dL−1). This altered physiological response due to fluid consumption could influence sport performance and should be considered. In addition, future sport and exercise studies should control for fluid consumption. 相似文献