#dna repair

[justkidneying]

Why we don't all have skin cancer from going outside

What is sunburn? Why does tanning give you skin cancer? The answer has to do with how UV rays fuck up your DNA.

There are three types of UV light: A, B, and C. UVC is absorbed in the atmosphere. UVA and UVB are what sunscreen protects against because they do the damage to your skin. Why do they do damage? UV light has a lot of energy, which can cause the bonds between molecules to change.

Onto DNA. This is the instructions for how to make you. It's made of nucleotides, four of them: Adenosine, Guanine, Cytosine, and Thymine. Thymine and Cytosine are what we call pyrimadines (the other two are called purines). Normally, in double-stranded DNA (that beautiful helix) a pyrimadine on one strand is paired with a purine from the other to make a "rung on the ladder" of dsDNA. (A goes to T and C goes to G).

What happens when UV light penetrates the skin and hits DNA? A pyrimadine dimer. So what this means is that two pyrimadines (usually Thymines) on the same strand have disconnected from their purines and bonded to each other. This creates a weird knob on the strand, and is a type of DNA lesion. Lesions can induce other mutations in the code. The dimer cannot be read by enzymes correctly either. This is all very bad, and can lead to cancer. Cancer = mutation

How do we fix this? So this is happening all the time. 100x per cell per second that your skin is exposed to sunlight. But we aren't all riddled with skin cancer because of Nucleotide Excision Repair. This is a form of DNA repair where the shitty nucleotides (the two bonded pyrimadines) are cut out. DNA polymerase synthesizes a new segment of DNA, and DNA ligase attatches it all back together. Now your DNA is fixed.

What happens when NER doesn't work? Very bad things. One condition where this repair pathway is impaired is Xeroderma pigmentosum. These people cannot repair damage from UV light and develop severe sunburns from only minutes in the sun. They will also get skin cancer and cataracts. Historically, people with this disease have been referred to as vampires, as they can only go out at night. Just shows how important your DNA repair mechanisms are and how much work they do around the clock.

[covenawhite66]

The team believes that gars have an unusually strong DNA repair apparatus. This allows the fish to correct somatic and germline mutations. They found that the gars’ DNA consistently evolves up to three times more slowly than any other major group of vertebrates.

[cbirt]

A team of UCSF, UCSD, and Brown University scientists has produced a multi-scale map of protein assemblies pertaining to damage response. The DNA Damage Response (DDR) makes sure that DNA replication, as well as transcription, are error-free. Disruptions in DDR cause several diseases. It is quite challenging to determine the proteins managing the DDR as well as their organization into several complexes, including constitutive interactions. The authors have addressed this challenge by systematically mapping DDR assemblies at multiple scales using multi-conditional network analysis. They performed a comprehensive screen for protein interactions on 21 DDR factors. They further incorporate existing proteomics data to construct a map of DDR protein assemblies, DDRAM. With a total of 605 proteins organized into a hierarchy of 109 assemblies, DDRAM also recovers canonical repair mechanisms and proposes new DDR-associated proteins.

A sophisticated network of machinery has evolved in organisms to guarantee the efficient operation of cells and to protect the integrity of the genome. This machinery is known as the DNA Damage Response (DDR). This machinery includes repair pathways that include different kinds of DNA lesions for direct reversal, base excision repair (BER), nucleotide excision repair (NER), mismatch repair (MMR), interstrand cross-link repair (ICL), and double-stranded break (DSB) repair. Apparatus for communicating the damage is also included in the DDR toolkit. The apparatus for damage sensing, signal transducers for communicating the damage to repair factors and downstream effectors, as well as connections to stress and apoptotic responses. DDR is also intertwined with cell-cycle checkpoints, chromatin packaging, and DNA replication. Through these processes, DDR involves thousands of gene expression and protein modification changes.

Continue Reading

[bryannellium-blog]

528Hz frequency which encourages us to restore human consciousness to its full power and potential is known as miracle tone, sensational tone, and frequency of transformation. Nasa scientists recorded that 528Hz resonates at the heart of the sun.

[biology-geology-beaches-india]

TSRNOSS, page 9.

[jcmarchi]

Cancer biologists discover a new mechanism for an old drug

New Post has been published on https://thedigitalinsider.com/cancer-biologists-discover-a-new-mechanism-for-an-old-drug/

Cancer biologists discover a new mechanism for an old drug

Since the 1950s, a chemotherapy drug known as 5-fluorouracil has been used to treat many types of cancer, including blood cancers and cancers of the digestive tract.

Doctors have long believed that this drug works by damaging the building blocks of DNA. However, a new study from MIT has found that in cancers of the colon and other gastrointestinal cancers, it actually kills cells by interfering with RNA synthesis.

The findings could have a significant effect on how doctors treat many cancer patients. Usually, 5-fluorouracil is given in combination with chemotherapy drugs that damage DNA, but the new study found that for colon cancer, this combination does not achieve the synergistic effects that were hoped for. Instead, combining 5-FU with drugs that affect RNA synthesis could make it more effective in patients with GI cancers, the researchers say.

“Our work is the most definitive study to date showing that RNA incorporation of the drug, leading to an RNA damage response, is responsible for how the drug works in GI cancers,” says Michael Yaffe, a David H. Koch Professor of Science at MIT, the director of the MIT Center for Precision Cancer Medicine, and a member of MIT’s Koch Institute for Integrative Cancer Research. “Textbooks implicate the DNA effects of the drug as the mechanism in all cancer types, but our data shows that RNA damage is what’s really important for the types of tumors, like GI cancers, where the drug is used clinically.”

Yaffe, the senior author of the new study, hopes to plan clinical trials of 5-fluorouracil with drugs that would enhance its RNA-damaging effects and kill cancer cells more effectively.

Jung-Kuei Chen, a Koch Institute research scientist, and Karl Merrick, a former MIT postdoc, are the lead authors of the paper, which appears today in Cell Reports Medicine.

An unexpected mechanism

Clinicians use 5-fluorouracil (5-FU) as a first-line drug for colon, rectal, and pancreatic cancers. It’s usually given in combination with oxaliplatin or irinotecan, which damage DNA in cancer cells. The combination was thought to be effective because 5-FU can disrupt the synthesis of DNA nucleotides. Without those building blocks, cells with damaged DNA wouldn’t be able to efficiently repair the damage and would undergo cell death.

Yaffe’s lab, which studies cell signaling pathways, wanted to further explore the underlying mechanisms of how these drug combinations preferentially kill cancer cells.

The researchers began by testing 5-FU in combination with oxaliplatin or irinotecan in colon cancer cells grown in the lab. To their surprise, they found that not only were the drugs not synergistic, in many cases they were less effective at killing cancer cells than what one would expect by simply adding together the effects of 5-FU or the DNA-damaging drug given alone.

“One would have expected that these combinations to cause synergistic cancer cell death because you are targeting two different aspects of a shared process: breaking DNA, and making nucleotides,” Yaffe says. “Karl looked at a dozen colon cancer cell lines, and not only were the drugs not synergistic, in most cases they were antagonistic. One drug seemed to be undoing what the other drug was doing.”

Yaffe’s lab then teamed up with Adam Palmer, an assistant professor of pharmacology at the University of North Carolina School of Medicine, who specializes in analyzing data from clinical trials. Palmer’s research group examined data from colon cancer patients who had been on one or more of these drugs and showed that the drugs did not show synergistic effects on survival in most patients.

“This confirmed that when you give these combinations to people, it’s not generally true that the drugs are actually working together in a beneficial way within an individual patient,” Yaffe says. “Instead, it appears that one drug in the combination works well for some patients while another drug in the combination works well in other patients. We just cannot yet predict which drug by itself is best for which patient, so everyone gets the combination.”

These results led the researchers to wonder just how 5-FU was working, if not by disrupting DNA repair. Studies in yeast and mammalian cells had shown that the drug also gets incorporated into RNA nucleotides, but there has been dispute over how much this RNA damage contributes to the drug’s toxic effects on cancer cells.

Inside cells, 5-FU is broken down into two different metabolites. One of these gets incorporated into DNA nucleotides, and other into RNA nucleotides. In studies of colon cancer cells, the researchers found that the metabolite that interferes with RNA was much more effective at killing colon cancer cells than the one that disrupts DNA.

That RNA damage appears to primarily affect ribosomal RNA, a molecule that forms part of the ribosome — a cell organelle responsible for assembling new proteins. If cells can’t form new ribosomes, they can’t produce enough proteins to function. Additionally, the lack of undamaged ribosomal RNA causes cells to destroy a large set of proteins that normally bind up the RNA to make new functional ribosomes.

The researchers are now exploring how this ribosomal RNA damage leads cells to under programmed cell death, or apoptosis. They hypothesize that sensing of the damaged RNAs within cell structures called lysosomes somehow triggers an apoptotic signal.

“My lab is very interested in trying to understand the signaling events during disruption of ribosome biogenesis, particularly in GI cancers and even some ovarian cancers, that cause the cells to die. Somehow, they must be monitoring the quality control of new ribosome synthesis, which somehow is connected to the death pathway machinery,” Yaffe says.

New combinations

The findings suggest that drugs that stimulate ribosome production could work together with 5-FU to make a highly synergistic combination. In their study, the researchers showed that a molecule that inhibits KDM2A, a suppressor of ribosome production, helped to boost the rate of cell death in colon cancer cells treated with 5-FU.

The findings also suggest a possible explanation for why combining 5-FU with a DNA-damaging drug often makes both drugs less effective. Some DNA damaging drugs send a signal to the cell to stop making new ribosomes, which would negate 5-FU’s effect on RNA. A better approach may be to give each drug a few days apart, which would give patients the potential benefits of each drug, without having them cancel each other out.

“Importantly, our data doesn’t say that these combination therapies are wrong. We know they’re effective clinically. It just says that if you adjust how you give these drugs, you could potentially make those therapies even better, with relatively minor changes in the timing of when the drugs are given,” Yaffe says.

He is now hoping to work with collaborators at other institutions to run a phase 2 or 3 clinical trial in which patients receive the drugs on an altered schedule.

“A trial is clearly needed to look for efficacy, but it should be straightforward to initiate because these are already clinically accepted drugs that form the standard of care for GI cancers. All we’re doing is changing the timing with which we give them,” he says.

The researchers also hope that their work could lead to the identification of biomarkers that predict which patients’ tumors will be more susceptible to drug combinations that include 5-FU. One such biomarker could be RNA polymerase I, which is active when cells are producing a lot of ribosomal RNA.

The research was funded by the Damon Runyon Cancer Research Fund, a Ludwig Center at MIT Fellowship, the National Institutes of Health, the Ovarian Cancer Research Fund, the Holloway Foundation, and the STARR Cancer Consortium.

[medicomunicare]

DNA repair going APE and strand breaks fixing with ATM: please no cash, just redox and contact bases

New research from a team of genome scientists and DNA damage response (DDR) experts breaks new ground in understanding the function of a protein currently limited in clinical trials for cancer treatments. The new investigaton shows how ATM-mediated signaling is induced by DNA single-strand breaks (SSBs) for DNA damage repair – illuminating the distinct mechanisms of SSB-induced ATM kinase and…

[simsezz]

MI - 528 Hz | pure tone | Solfeggio Frequency | Transformation, Love and Miracles (DNA Repair)

[fcmuzik]

528 Hz Healing Frequency: Repair DNA, Inspire Change, Miracle Tone - Pro...

[multidimensional-p]

Just for Today, 6/2/23: Present P Power 🌳🌺

Right Now is powerful.

[chessbird]

iteratorsona and his two eepers

[get-starfingered]

So glad the fandom has no control over the canon of this series, istg these takes are so bland and would ruin Jojo's.

[jcmarchi]

Nanoparticles Deliver Treatment Directly to Tumors of Deadly Brain Cancer - Technology Org

New Post has been published on https://thedigitalinsider.com/nanoparticles-deliver-treatment-directly-to-tumors-of-deadly-brain-cancer-technology-org/

Nanoparticles Deliver Treatment Directly to Tumors of Deadly Brain Cancer - Technology Org

Using nanoparticles administered directly into the cerebrospinal fluid (CSF), a research team has developed a treatment that may overcome significant challenges in treating a particularly deadly brain cancer.

The researchers, led by professors Mark Saltzman and Ranjit Bindra, administered to mice with medulloblastoma a treatment with specially designed drug-carrying nanoparticles. The study, published in Science Translational Medicine, showed that mice who received this treatment lived significantly longer than mice in the control group. 

Medulloblastoma, a brain cancer that predominantly affects children, often begins with a tumor deep inside the brain. The cancer is prone to spread along two protective membranes known as the leptomeninges throughout the central nervous system, particularly the surface of the brain and the CSF. Leptomeningeal spread is seen in a number of primary brain tumors, as well as in brain metastases from solid tumors in the breast, lung, and other places. Because there are no anatomic barriers in the CSF to prevent further growth, these cancers can spread rapidly.  

Targeting tumors in the CSF has proven difficult, in part because the fluid rapidly cycles through the central nervous system about four times a day in humans, typically flushing away anti-tumor drugs before they’ve had a chance to accumulate and have any effect. 

“It’s like a waterfall system, with a fast, rapid fluid flow,” said Minsoo Khang, lead author of the study and a former graduate student in Saltzman’s lab. 

To overcome this obstacle, the research team fabricated nanoparticles that adhere to tumors. Designed in Saltzman’s lab, these nanoparticles are made with degradable polymers that slowly release a DNA repair inhibitor, talazoparib, which is FDA-approved and currently used in the clinic for a number of cancers. The drug is one of a relatively new class of cancer drugs known as PARP inhibitors, which block an enzyme that helps repair DNA. Without the ability to repair their DNA, tumor cells are more likely to die.   

The nanoparticle treatment is injected intrathecally – that is, it’s delivered directly between the leptomeninges protecting the CSF. Over a period of weeks, the researchers detected the presence of the nanoparticles in the CSF for as long as 21 days after a single dosing. 

“We were very excited to have found a medium that has long-term retention in this fluid space, which is otherwise challenging,” Khang said.  

Treating brain cancers in general is challenging since few treatments can penetrate the blood-brain barrier, a natural defense system that can block potentially helpful drugs. The research team’s method could offer a solution. 

“There’s been very little work on intrathecal delivery of nanoparticles, so we’re very excited because it can allow us to go after the leptomeningeal spread of disease from brain metastases,” said Bindra, the Harvey and Kate Cushing Professor of Therapeutic Radiology and Professor of Pathology. “This has really opened up an entirely new way to treat these patients, although much more work needs to be done.”

Using the nanoparticles to target the tumors allowed the researchers to use the drug talazoparib, which has proven to be effective in a number of solid tumors outside of the brain. Because the drug has limited to no penetration of the central nervous system, however, an orally delivered dose would have limited efficacy against tumors with leptomeningeal spread.

“By encapsulating it in a nanoparticle and directly injecting it into the CSF, we now get very high exposure in just that area,” said Saltzman, the Goizueta Foundation Professor of Biomedical Engineering, Chemical & Environmental Engineering & Physiology, and a member of Yale Cancer Center. 

Delivering the drug intrathecally also avoids injecting it directly into the brain, a technique referred to as convection-enhanced delivery. This very challenging procedure can be performed only a few times a year. Intrathecal injections, in contrast, are much less invasive and can be given without a hospital stay. 

“This is huge for us, because now we can do multiple nanoparticle treatments over time,” Bindra said.

In addition to the nanoparticle injection, mice were also given an oral dose of a chemotherapy drug known as temozolomide. 

“It’s a new platform where we can give these oral chemotherapies that get across the blood-brain barrier and a targeted agent just in the central nervous system,” Bindra said. “In essence, this compartmentalization of combination therapy will enhance synergistic tumor cell killing while minimizing systemic toxicity.” 

The mice that received the nanoparticle-based treatment lived significantly longer than the mice who received drug therapy that didn’t use nanoparticles and even longer than the mice that received no treatment. Further, there was much less cancer spreading in the mice that received the drug-carrying nanoparticles. 

The researchers said the next steps will be to validate the approach in larger animal models, eventually followed by human testing. The team also plans to test the treatment method on other cancers, particularly those that tend to spread to the brain.  

Source: Yale University

You can offer your link to a page which is relevant to the topic of this post.

[godsprettiestprincess]

*accidentally spread misinformation voice* I just want to clarify, as unfortunate as it is, Jedikiah and Irene do not actually brain meld in canon. He does drug her unconscious and steal her powers, but the timeline in which he both gifts her someones else’s powers so she gets them back and gives himself brain damage so his own brain radio-signal thing is rewritten into hers & links them irrevocably only exists in my brain.

[lilacerull0]

mechanic/healer/repair system of the world...