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The DNA mismatch repair operates in a defined time window

Nessun commento December 30, 2011 No comments

In eukaryotes, the vast group of organisms that includes humans, appears to be essential to the survival ability of certain proteins to repair genetic errors that occur when DNA is replicated shortly before cell division, and do it quickly and accurate.

In a paper recently published in the journal Science, researchers at the Ludwig Institute for Cancer Research and the San Diego School of Medicine parzalmente have solved the mystery of how these proteins perform their tasks in respect of the nitrogenous base mismatches (mismatch) that can take over with the replication, in a process known as DNA mismatch repair ( MMR ).

One of the most important questions to answer is how the MMR proteins can discriminate which of the two bases of a mismatch is the "right" and what that "wrong".

says Christopher D. Putnam, a member of the team that conducted the research.

For example, if a guanine (G) after replication is paired (incorrectly) with a thymine (T), where is the error? In G or T in? If the repair mechanism removes the base originally present in the DNA template, instead of the erroneously incorporated, it will result in a mutation, not a repair!

MSH2-MSH6 heterodimers eukaryotic protein homologous to bacterial MutS recognize mismatches on the genome and initiate their repair

Using the model organism Saccharomyces cerevisiae, ie baker's yeast, researchers led by Richard D. Kolodner have found that the newly synthesized DNA strand carries a permanent signal for 10-15 minutes after the replication, which marks it as well as new and potentially "wrong" in the eyes of the mechanism of MMR.

The precise nature of this signal, however, has not been identified, and the main assumptions are the presence of nicks (cuts single-stranded) on the newly synthesized strand, or the association on the same of specific proteins associated with replication.

This discovery, published in the past combined with the first work that shows the action mechanism of MMR in vivo , adds a further piece of knowledge in how eukaryotes eliminate errors in DNA replication, mechanisms closely to fight or to ' onset of cancer.

As eukaryotes marchino the newly synthesized DNA strands is a mystery that has lasted 30 years - Putnam says - but such work makes very clear ideas about how the mechanism of mismatch repair functions.

Source: Science
Review MMR in eukaryotes - JBC.org
Categories: Biology

The replication of bacteria magnetotattici: split sleeves

Nessun commento December 21, 2011 No comments

The bacteria magnetotattici are a particular class of micro-organisms described for the first time by Richard Blakemore in the 70, equipped with the special feature to orient themselves along the lines of the earth's magnetic field.

These response properties may help to magnetism marine bacteria that live in conditions of low oxygen in the water and sediments and navigate to "orient" in an environment where the levels of essential nutrients such as sulfides and ossideno change drastically with the depth, as stated by Dirk Schüler, a microbiologist at the Ludwig-Maximilians University of Monaco.

The bushes of these bacteria are made ​​up of small organelles called magnetosomi, which contain crystals of magnetite (Fe 3 O 4), greigite (Fe 3 S 4) and other magnetic minerals: the magnetic field produced by a single magnetosoma however, is not sufficiently strong to orient the microbe to the terrestrial field, so these organelles are joined together in a chain to form a stronger magnet.

The problem takes over when the cells are replicated: normally the bacteria are divided by a longitudinal initial growth, and then synthesize new cell wall in the internal side of the central zone, the so-called furrow of division, which accrescendosi sinks more and more in the cytoplasm , closing as a loop, until the edges of the wall do not connect newly synthesized and the two new bacteria are detached. The force generated by the wake of division is not alone sufficient, Schüler says, to "unplug" magnetosomi chains that attract like magnets.

Thus the bacteria magnetotattici have a dual problem in the process of replication: able to overcome the internal magnetic forces that tend not to separate the two future daughter cells, and at the same time be able to distribute evenly the organelles magnetic transfer for the selective advantage of the sensitivity Magnetic both new cells.

The angle taken by the next two daughter cells weakens the internal magnetic resistance. In red are the chains magnetosomi.

Using light and electron microscopy techniques, the team Schüler has followed in real time the division into two daughter cells of the bacterium Magnetospirillum gryphiswaldense, a paradigm of the class of bacteria magnetotattici. Initially, the division process has followed the classic lineup of the bacterial division: after genome replication, the cell began to elongate and then to taper gradually into the central area.

At this point the news: the fact magnetosomi begin to migrate toward the center and accumulate at the cleavage furrow through the interaction with actin-like cytoskeletal proteins, so the two future daughter cells assume an angle with respect the other of about 50 degrees, and finally separate quickly. The apparent "fold" assumes that the dividing cell appears to be due to the fact that the groove of division is increased (toward the inside of the cell) in an asymmetrical manner, which results in an imbalance of forces on one of the two sides, bringing the two "half-cylinders" which constitute the daughter cells to tilt between them.

Why do all this work to separate the two daughter cells? Simply giving a detour because of this kind can weaken the magnetic forces between magnetosomi accumulated in the cleavage furrow, and then divide evenly between the two new cells, the precious organelles.

The energy required to detach the chains magnetosomi, imparting a bending of this type, is the order of 10 piconewtons, which is normally equivalent to the force generated during the binary fission bacterial

Schüler says. So M. gryphiswaldense does is use the normal energy required for cleavage, simply by optimizing the "geometry" of the division to be able to beat its internal electrical resistance.

Source: Molecular Microbiology
Categories: Biology

Unveiling the mystery of the mole that feels no pain

Nessun commento December 19, 2011 No comments

Naked mole-rats, native of East Africa, in addition to unique scientific name ( Heterocephalus Glaber ), is not lacking in extravagant biological characteristics: living underground in conditions of semi-darkness, is hairless, has a life expectancy of more than twenty 'year, more unique than rare among rodents, and do not hardly ever get sick of cancer .

She was recently unveiled its yet another particular feature, or insensitivity to pain caused by acid: this kind of adaptation allows moles to thrive in the underground tunnels that form their colonies, despite the presence of high levels of acidity due to ' accumulation of carbon dioxide emitted to the death of the animals.

A better understanding of how the pain pathway is a key step in the development of new ways to treat pain

Ewan Smith says St. John, the manager of the new study, neuroscientist at the Max Delbrück Center for Molecular Medicine in Berlin.

Close up of curious (how ugly) naked mole-rat

Smith and his colleagues had previously discovered that injecting small amounts of hydrogen in the paw of a mole-rats did not had any reaction by the animal. In contrast, mice subjected to the same treatment immediately portrayed his paw and began to lick: just to get an idea of ​​the kind of pain administered, think of what a man can feel if you put lemon juice on a wound.

It 'well known that the acid is perceived through the nociceptors, a particular class of receptors present on nociceptive neurons, or those sensors Members to collect external stimuli potentially harmful to the body and to transmit to the central nervous system to initiate the response of pain. These receptors are ion channels that "perceive" the presence of acids through a response to high concentrations of protons (which are derived from acidic conditions) by opening up and stimulating the neuron. Smith is therefore expected that by analyzing the neurons of the mole would not find the receptors for the acid, or would have found a non-functional but showed that the mole-rats have the same nociceptors of mice, and with the same functionality.

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Categories: Biology , Neuroscience

Bacteria possess an acquired immune system

1 commento October 24, 2010 a comment
This is probably one of the most important discoveries of the last ten years, in molecular biology.

A new study from Rice University has determined a mathematical model to describe a system of acquired immunity in bacteria, able to fight infection by bacteriophages.

Bacteriophages are viruses that specifically attack the bacteria, their mechanism of action is based on the injection of their genome within the host, in order to reproduce exploiting its molecular machinery. It seems that the bacteria, however, have developed a system to immunize from some of these potential threats.

Hypothetical mechanism of action of CRISPR

The research focused on the region CRISPR ("clustered interspaced short palindromic repeats Regularly") of bacterial DNA. It consists of two types of sequences: the first, which gives its name to the region and that had initially attracted the scientific interest, contains short repeats in the second, initially identified as DNA spacer between repeats, contains specific genetic sequences of phages.

When a sequence of a phage is located in the region CRISPR, the bacterium is immunized by infection of the phage, as it becomes able to recognize and degrade the viral genome, in a manner analogous to the process of RNA interference ( RNAi ) of eukaryotic organisms .

"From a purely scientific perspective, this research tells us that things would not even have imagined just a few years ago, but there is also a practical interest in this work," said Michael Deem, Professor of Biochemistry, Genetic Engineering, Physics and Astronomy at Rice University.

In essence, the CRISPR acts storing a set of fragments of the genomes of these viruses that attack the bacteria, which takes place by means of suitable storage protein complexes that act once they enter in contact with exogenous genetic material. So it turns out to be heritable, when the bacterium divides, but also programmed during the life of the organism. The CRISPR may contain from thirty to fifty different fragments, which imply the resistance against many types of phage.

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Categories: Biology

The new and promising therapy "antigenic"

Nessun commento October 22, 2010 No comments
The therapy is based on the formation of triple helices of DNA and light energy to silence gene activity

The antigenic therapy is an innovative treatment strategy which provides for the use of DNA-based drugs to precisely locate the light energy on a target gene, thus turning off its activity.

A recently published review of Oligonucleotides, a peer-reviewed journal published by Mary Ann Liebert, Inc. of New Rochelle (New York), analyzes the opportunities and challenges for the clinical application of this new approach through modulation of DNA photo-activation. The review can be viewed for free at segnente link (Site-Specific DNA Photocleavage by Oligonucleotide Conjugates and Photomodulation)

Formation of a triple helix of DNA by the insertion of a oligont. in the major groove

Netanel Kolevzon and Eylon Yavin, of The Hebrew University of Jerusalem (Israel), in their article describing the mechanism that undergirds antigen and development of drugs based on TFO (which stands for Triple Forming Oligonucleotide), capable of inhibiting the expression gene in a highly focused and selective.

The TFO are in fact oligonucleotides (synthetic) capable of forming a triple helix, introducing in the major groove of the double helix and creating type Hoogsteen hydrogen bonds with the purine of the pairs of Watson-Crick base ¹ : Unlike antisense therapies already existing, that target RNA, therapy has therefore as antigenic targets directly on a DNA sequence.

By attaching a photoreactive agent TFO oligonucleotide, and providing light energy to the attachment site on the genome, the drug (light sensitive) is activated and triggers a cleavage or cross-linking of DNA, that damage to the genome, photo- induced and site-specific, will result in gene silencing.

"Many obstacles lie ahead before this strategy can be applied clinically," the authors warn. In any case, if the therapy will prove antigenic actually valid "many diseases that are currently incurable or otherwise treatable with poor results, could be potential applications of this kind of approach," they conclude.

"This is a clever and potentially very effective approach for regulating targeted gene expression," says John Rossi, PhD, co-editor of Oligonucleotides and Professor at the Department of Molecular Biology, Beckman Research Institute (California)
Sources: PhD in Biotechnology Stefano D'Errico , University of Naples Federico II
Liebertpub.com
Categories: Biotech , Medicine and Health

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