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Nitchakan Chaiprukmalakan

New study: Tracking proteins that repair DNA - 0 views

  • DNA damage could be caused by many things including toxins, radiation, or a failure in molecular chemistry. If it happens in one cell, the damage may do nothing, or at worse cause the cell to die. If damage occurs in a reproductive cell (a zygote) it can be an inherited mutation; the consequences of which can go on for generations
  • The DNA repair workers are (so far as we know) protein molecules.
  • Under microscopic observations it was seen that the UvrA protein randomly jumps from one DNA molecule to the next, staying about 7 seconds before moving on. However, when UvrA formed a complex with two UvrB molecules (UvrAB), the search became more sophisticated and slower. The complex would slide along the DNA strand for as long as 40 seconds before moving to another molecule. Sometimes it was observed that the UvrAB motion would ‘pause,’ apparently checking for structural abnormalities that might indicate DNA damage.
  • ...1 more annotation...
  • It’s assumed the protein complex is analyzing, but the mechanism of analysis is unknown. It’s also unknown if the UvrAB complex (or similar complex) actually does the repair, or if it signals for some other protein complex(es) to make the repair.
Sasicha Manupipatpong

Gene switches do more than flip 'on' or 'off': Can exhibit much more complex binding be... - 1 views

  • right genes for the job are turned on only in the specific cells where they are needed
  • molecular "clutch" that converts treadmilling to a stable bound state, moving the transcription process forward to completion to turn the gene on
  • act like a switch; they are either "on" (bound to DNA) or "off" (not bound)
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  • can exhibit much more complex binding behavior
  • transcription factors' binding process is dynamic and involves more than just being bound or unbound
  • In addition to a stable binding state (on or off)
  • "treadmilling," where no forward transcription process is occurring
  • indicator of whether a gene was turned on or off
  • measure and calculate how long a protein is associated with all of the different genes it regulates
  • proteins that bind in the stable state are associated with high levels of gene transcription
  • if we can regulate the transition between treadmilling and stable binding, we can regulate the outcome in terms of gene expression
  • genetic medicine -- a new way to regulate the 'switches' that turn gene expression associated with disease on or off.
  • measured how long it took the competitor transcription factor to replace the resident protein and used this data to calculate the residence time at each location in the genome
  • specific proteins called "transcription factors" that control which genes are turned on or off in cells by binding to nearby DNA
  • new insights on how cells respond to developmental cues and how they adapt to changing environmental conditions
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    Genes have been discovered to be more complex than we previously thought--rather than having only on and off states, there is an intermediate state called "treadmilling".
Rafael Chen

Scientists develop tools to make more complex biological machines from yeast - 0 views

  • creating a new type of biological "wire," using proteins that interact with DNA and behave like wires in electronic circuitry
  • it can be re-engineered over and over again
  • fundamental DNA components, called "promoters," which are needed for re-programming yeast
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  • Future applications of this work could include tiny yeast-based machines that can be dropped into water supplies to detect contaminants, and yeast that records environmental conditions during the manufacture of biofuels to determine if improvements can be made to the production process.
  • help to improve things such as pollution monitoring and cleaner fuels
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    Scientist uses yeast as the foundations in making more complex biological machines through genetic engineering.
Nitchakan Chaiprukmalakan

Missing Lincs - Science News - 6 views

    • Nitchakan Chaiprukmalakan
       
      Scientists are finding more information about the importance of the non coding RNAs, lincRNAs.
  • Only now have scientists begun identifying the previously invisible contractors who make sure that materials get where they are supposed to be and in the right order to build a human being or any other creature. Some of these little-known workers belong to a class of molecules called long intergenic noncoding RNAs.
  • And the lincRNAs originate in what scientists used to view as barren wastelands between protein-coding genes. But new research is showing that these formerly underappreciated workers have important roles in projects both large and microscopic.
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  • In the last few years, scientists have learned that lincRNAs, as well as other RNAs that are long and noncoding but not intergenic, perform a variety of jobs. Some serve as guides showing proteins where to go, while others tether proteins to different types of RNA, or to DNA. Some work as decoys, distracting regulatory molecules from their usual assignments. Some may even have multiple roles, all the while chattering away to other RNA within cells. (It is not idle gossip; RNA communication within cells may ward off diseases such as cancer.) And as the ultimate multitaskers, lincRNAs keep proper cellular development ticking along and help define what makes mice mice and people people.
  • That archive contains about 3 billion genetic letters, far more than the genomes of less complex organisms such as roundworms and fruit flies.
  • In 2005, the research revealed that even though genes that code for proteins make up only 1.5 percent of the mouse genome, more than 63 percent of the genome’s DNA is copied into RNA. In humans the number is even higher, with up to 93 percent of the genome made into RNA, even though protein-coding genes make up less than 2 percent of the genome.
  • At first, many scientists didn’t know what to make of the excess RNA. Some thought it was overexuberance on the part of the DNA-copying machinery. But gradually researchers began to realize that many of those extra RNAs had important jobs to do.
  • Some, though, appear to act like general contractors — not hammering in the nails and pouring the foundations of cells themselves, but dictating how the job should be done.
  • One of the most famous long noncoding RNAs, known as XIST, is also one of the most hands-on. XIST is in charge of shutting down one of the X chromosomes in every single cell of women and girls
  • XIST doesn’t have a long commute to work; it coats whichever X chromosome makes it, preventing other genes on the chromosome from being activated
  • One of the most well-studied linc­RNAs, named HOTAIR, wasn’t lucky enough to get a job close to home. It is copied from DNA on chromosome 12 but has to travel to chromosome 2 to shut down several genes in a group known as the HOXD cluster, genes important for proper development of an organism
  • Not only does HOTAIR help direct development, but it is also important throughout life to help cells pinpoint their location in the body.
  • Whether promoting health or mis­directing cells, lincRNAs don’t necessarily act alone.
  • A lincRNA known as HOTTIP also works with a crew of histone modifiers, but instead of shuttering genes, HOTTIP’s crews hang grand-opening signs to attract gene-activating machinery
  • In the recipe for humans, lincRNAs are in the thick of things from the very beginning. At least 26 different lincRNAs need to be on to keep an embryonic stem cell a stem cell
  • Just how lincRNAs choose which genes to turn on and off isn’t yet known. But Pier Paolo Pandolfi, a geneticist at Beth Israel Deaconess and Harvard Medical School, suspects that the lincRNAs are whispering to each other and to other RNAs, keeping tabs on all a cell’s goings-on. Pandolfi laid out his hypothesis for how this chatter might help control protein production and other processes in the Aug. 5 Cell.
  • The Columbia team and Pandolfi’s team independently found that tweaking levels of a few messenger RNAs that distract microRNAs from PTEN messenger RNA can lead to prostate cancer or a type of brain tumor called glioblastoma. Just messing with levels of a messenger RNA from another gene known as ZEB2 throws off PTEN protein levels and can lead to melanoma in mice, Pandolfi’s group reported in another paper in the Oct. 14 Cell.
  • Losing one noncoding RNA may be disastrous for a cell, but for want of noncoding RNAs whole species may never have evolved, argues Queensland’s Mattick. He and others say the real function of lincRNAs is to give evolution a sort of molecular clay from which to mold new designs.
  • Humans have several lincRNAs that are found in no other species. Many of those RNAs are made in the brain, leading scientists to speculate that the molecules may be at least partially responsible for that important organ’s evolution.
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    Is RNA the most important molecule in the cell? There is a lot of evidence leading to new understandings of RNA and it's role in many different mechanisms within a cell.
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