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Termination Stage in Biacteria

Posted by star on 2018-09-03 01:48:00
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    The two replication forks initiated from oriC (min 84) eventually meet at a termination region on the opposite side of the chromosome, triggering a series of events that lead to completion of chromosome synthesis and then chromosome separation. The movement of the replication fork within the termination region is arrested or at least forced to pause for a long time at specific termination sites (Ter sites). Ter sites are conserved 11 bp sequences that may be present in two orientations. When present in one orientation, they allow the replication machinery to pass through but when present in the opposite orientation they stop replication. E. coli has a total of ten Ter sites that are present in two clusters, each containing five Ter sites. The TerC, TerB, TerF, TerG, and TerJ block the progress of a replication fork that moves in a clockwise direction. Whereas TerA,TerD,TerE,TerI, and TerH block the progress in the opposite direction.

 

    A protein called the terminus utilization substance (Tus) binds to the Ter sites. The Tus protein binds to Ter as a monomer with a very high affinity, ensuring the polar function of the Tus·Ter complex. When present in the proper orientation, the Tus ·Ter complex arrests the progress of the replication fork by interfering with DnaB helicase's ability to unwind DNA at the replication fork. The gene that encodes the Tus protein, tus, is located at minute 36.3 so Jies within the termination region. The physiological significance of the Tus · Ter system remains an open question because null mutants lacking the Tus protein grow normally under a variety of growth conditions. Bacillus subtitis uses an entirely different protein in place of Tus, one that acts as a dimer to bind to termination sites that ar......

Mild air pollution can also affect the heart

Posted by star on 2018-09-02 19:16:29
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     A new study in the UK found that long-term exposure to mild air pollution can also affect the heart, leading to heart changes similar to the early stages of heart failure.

     The researchers analyzed data from a long-term survey in the UK involving about 4,000 volunteers. These volunteers answered questions about lifestyles and other aspects of the survey and accepted tests for heart and blood.

     The results of Association Between Ambient Air Pollution and Cardiac Morpho-Functional Phenotypes published in the new issue of Circulation show that those who live near the road and are exposed to nitrogen dioxide or PM2.5 (fine particulate matter) for a long time are more prone to left and right ventricular hypertrophy. Moreover, the more serious the air pollution, the more obvious this problem of ventricular hypertrophy. Similar heart changes can also be observed in the early stages of heart failure.

     It is worth mentioning that the annual average level of air pollution in the environment in which these volunteers are located is within the recommended level of the UK, which is less than 25 micrograms per cubic meter.

     The researchers said that this is only an observational study, and cannot lead to causal conclusions. But people have seen that in even mild air pollution, the heart structure will change significantly, which means that mild air pollution may also affect health. The results of the study once again remind people to pay attention to air pollution control and self-protection.



DNA clamp loader

Posted by star on 2018-08-31 02:15:51
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    The clamp loader uses energy provided by ATP to load the sliding clamp onto a DNA template primer with a 5'-overhang. It exists as a subassembly of the DNA polymerase Ⅲ holoenzyme and also in a free form. The free form does not appear to arise from the dissociation of the holoenzyme because (1) the. Holoenzyme is stable when studied in vitro and can only be dissociated under harsh nonphysiological conditions and (2) the two forms have different subunit compositions: γ3δδ'ΧΨ in the free form and τ2γδδ'ΧΨ in the holoenzyme. Differences between the two forms are not as great as they may at first appear because both γandτsubunits are encoded by the same dnaX gene. Theτsubunit is the full-length product while theγsubunit is a truncated form that is missing about 1/3 of the residues at the C-terminus. The C-terminal region, which is present inτbut notγ, plays an important function in DNA polymerase Ⅲholoenzyme because it contains the site that binds the core polymerase and DnaB helicase.

    Mike O'Donnell and coworkers obtained considerable information about clamp loader structure and function by studying the structure and functions of aγ3δδ' complex they constructed by combining subunits in vitro. Thisγ3δδ' complex is called the minimal clamp loader because it is the smallest complex that can load sliding clamps onto DNA. Neither the Χ or Ψ subunit is required to load the clamp.

    The Ψ subunit stabilizes the clamp loader and the X subunit displaces primase from SSB. O'Donnell and coworkers obtained an important clue to the minimal clamp loader's mechanism of action by studying the effect that the δ subunit has on the sliding clamp. In one key experiment, t......


    Although data generated from autoradiography and electron microscopy experiments show that leading and lagging strand synthesis are coordinated, it was difficult to see how the replication machinery could coordinate the synthesis, because DNA polymerases at the replication fork must move in opposite directions along the two antiparallel DNA template strands.

    In 1980, Bruce Alberts proposed the trombone model of replication to explain how coordination of replication of leading and lagging strands might take place. The polymerase cycle on the replication fork is in an updated version of this model, the lagging strand of template DNA loops out as each Okazaki fragment is formed. This looping allows the pair of core polymerase subassemblies to coordinate leading and lagging strand synthesis while moving in opposite directions along their template strands. Okazaki fragment formation avoids the problem of forming very long lagging strand loops and permits the trombone loop to be reset after each Okazaki fragment has been completed. At the time that Alberts proposed the trombone model, relatively little was known about DNA polymerase Ⅲ holoenzyme structure. However, the discovery that each holoenzyme contains two core polymerase subassemblies seems to fit the trombone model and explains how the DNA replication machinery coordinates leading and lagging strand synthesis at the replication fork.

    A great deal is now known about the events that take place during Okazaki fragment formation. Primase (DnaG) initiates the synthesis of the Okazaki fragment by synthesizing an RNA primer that is about 10 to 12 nucleotides long. Primase interacts with the DnaB helicase at the start of primer synthesis but the two pull apart as they move in opposite directions along the lagging strand template ; primase moves in a 3'→5'direction and helicase in a 5'→3'direction.

    The clamp loa......

Acetyl-L-carnitine can be used as a biomarker for depression

Posted by star on 2018-08-30 19:31:41
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The latest research shows that the level of acetyl-L-carnitine in the blood of depressed patients is low. As a biomarker of depression, this chemical promise to open up new antidepressants that work faster.

Acetyl-L-carnitine is a common human chemistry that is abundant in muscles and brain and is an important mediator of systemic fat metabolism and energy production. In the brain, acetyl-L-carnitine plays an important role in the inhibition of excessive activation of excitatory neurons in the hippocampus and frontal cortex.

The Acetyl-l-carnitine deficiency in patients with major depressive disorder published in the PNAS shows that the level of acetyl-L-carnitine in the blood of depressed patients is significantly lower than that of healthy people. Blood acetyl-L-carnitine levels are particularly low in patients with severe depression and in patients with early onset of depression.

Previous studies have found that oral or intravenous acetyl-L-carnitine can reverse the depressive symptoms of mice, and the symptoms of depression in mice can be improved within a few days. Currently commonly used antidepressants take 2 to 4 weeks to work in animal experiments and human patients.

In the pharmacy, acetyl-L-carnitine is often sold as an over-the-counter health product. Researchers remind the public not to buy it for the treatment of depression. Acetyl-L-carnitine is currently an important biomarker for depression, and whether supplementation of this substance can help improve the symptoms of people with depression requires large-scale clinical studies.



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