Enzyme Mechanism Corrects Cellular DNA Damage
|
By LabMedica International staff writers Posted on 16 Oct 2017 |
|
Image: An illustration of a TOP2 DNA-protein cross-link (TOP2cc in magenta) bound to DNA (Photo courtesy of Dr. Scott Williams).
Researchers have identified a mechanism used by cells to correct damage to their DNA caused by chemotherapeutic drugs and some antibiotics.
The enzyme topoisomerase 2 (TOP2) creates DNA double-strand breaks in order to regulate DNA topology and is critical for processes such as replication and transcription. A covalent complex between TOP2 and DNA (TOP2cc), which impedes the activity of the topoisomerase, is an intermediate in the reaction that can be trapped by drugs.
In a recent study, investigators at the [U.S.] National Institutes of Health/National Institute of Environmental Health Sciences (Bethesda, MD, USA) reported in the September 29, 2017, online edition of the journal Science that the SUMO ligase enzyme ZATT promoted the resolution of TOP2cc by means of another enzyme, tyrosyl-DNA phosphoesterase 2 (TDP2), both by enhancing recruitment of TDP2 to SUMOylated TOP2 and by enhancing the hydrolase activity of TDP2.
SUMO (Small Ubiquitin-like Modifier) proteins are a family of small proteins that are covalently attached to and detached from other proteins in cells to modify their function. SUMOylation is a post-translational modification involved in various cellular processes, such as nuclear-cytosolic transport, transcriptional regulation, apoptosis, protein stability, response to stress, and progression through the cell cycle. SUMO proteins are similar to ubiquitin, and SUMOylation is directed by an enzymatic cascade analogous to that involved in ubiquitination. In contrast to ubiquitin, SUMO is not used to tag proteins for degradation.
"In this study, we discovered a new molecular disarmament apparatus for these cell-killing bombs (TOP2cc)," said senior author Dr. Scott Williams, deputy chief of the genome integrity and structural biology laboratory at the National Institute of Environmental Health Sciences. "ZATT is like a bomb sniffing dog, so when it locates its target, it sounds an alarm to mobilize the recruitment of TDP2, which cuts the red wire to disarm these threats."
Related Links:
[U.S.] National Institutes of Health/National Institute of Environmental Health Sciences
The enzyme topoisomerase 2 (TOP2) creates DNA double-strand breaks in order to regulate DNA topology and is critical for processes such as replication and transcription. A covalent complex between TOP2 and DNA (TOP2cc), which impedes the activity of the topoisomerase, is an intermediate in the reaction that can be trapped by drugs.
In a recent study, investigators at the [U.S.] National Institutes of Health/National Institute of Environmental Health Sciences (Bethesda, MD, USA) reported in the September 29, 2017, online edition of the journal Science that the SUMO ligase enzyme ZATT promoted the resolution of TOP2cc by means of another enzyme, tyrosyl-DNA phosphoesterase 2 (TDP2), both by enhancing recruitment of TDP2 to SUMOylated TOP2 and by enhancing the hydrolase activity of TDP2.
SUMO (Small Ubiquitin-like Modifier) proteins are a family of small proteins that are covalently attached to and detached from other proteins in cells to modify their function. SUMOylation is a post-translational modification involved in various cellular processes, such as nuclear-cytosolic transport, transcriptional regulation, apoptosis, protein stability, response to stress, and progression through the cell cycle. SUMO proteins are similar to ubiquitin, and SUMOylation is directed by an enzymatic cascade analogous to that involved in ubiquitination. In contrast to ubiquitin, SUMO is not used to tag proteins for degradation.
"In this study, we discovered a new molecular disarmament apparatus for these cell-killing bombs (TOP2cc)," said senior author Dr. Scott Williams, deputy chief of the genome integrity and structural biology laboratory at the National Institute of Environmental Health Sciences. "ZATT is like a bomb sniffing dog, so when it locates its target, it sounds an alarm to mobilize the recruitment of TDP2, which cuts the red wire to disarm these threats."
Related Links:
[U.S.] National Institutes of Health/National Institute of Environmental Health Sciences
Platinum Member
COVID-19 Rapid Test
OSOM COVID-19 Antigen Rapid Test
Complement 3 (C3) Test
GPP-100 C3 Kit
New
Gold Member
Fully Automated Cell Density/Viability Analyzer
BioProfile FAST CDV
Latest BioResearch News
- Genome Analysis Predicts Likelihood of Neurodisability in Oxygen-Deprived Newborns
- Gene Panel Predicts Disease Progession for Patients with B-cell Lymphoma
- New Method Simplifies Preparation of Tumor Genomic DNA Libraries
- New Tool Developed for Diagnosis of Chronic HBV Infection
- Panel of Genetic Loci Accurately Predicts Risk of Developing Gout
- Disrupted TGFB Signaling Linked to Increased Cancer-Related Bacteria
- Gene Fusion Protein Proposed as Prostate Cancer Biomarker
- NIV Test to Diagnose and Monitor Vascular Complications in Diabetes
- Semen Exosome MicroRNA Proves Biomarker for Prostate Cancer
- Genetic Loci Link Plasma Lipid Levels to CVD Risk
- Newly Identified Gene Network Aids in Early Diagnosis of Autism Spectrum Disorder
- Link Confirmed between Living in Poverty and Developing Diseases
- Genomic Study Identifies Kidney Disease Loci in Type I Diabetes Patients
- Liquid Biopsy More Effective for Analyzing Tumor Drug Resistance Mutations
- New Liquid Biopsy Assay Reveals Host-Pathogen Interactions
- Method Developed for Enriching Trophoblast Population in Samples
Channels
Clinical Chemistry
view channel
3D Printed Point-Of-Care Mass Spectrometer Outperforms State-Of-The-Art Models
Mass spectrometry is a precise technique for identifying the chemical components of a sample and has significant potential for monitoring chronic illness health states, such as measuring hormone levels... Read more.jpg "Image: Reaching speeds up to 6,000 RPM, this centrifuge forms the basis for a new type of inexpensive, POC biomedical test (Photo courtesy of Duke University)")
POC Biomedical Test Spins Water Droplet Using Sound Waves for Cancer Detection
Exosomes, tiny cellular bioparticles carrying a specific set of proteins, lipids, and genetic materials, play a crucial role in cell communication and hold promise for non-invasive diagnostics.... Read more
Highly Reliable Cell-Based Assay Enables Accurate Diagnosis of Endocrine Diseases
The conventional methods for measuring free cortisol, the body's stress hormone, from blood or saliva are quite demanding and require sample processing. The most common method, therefore, involves collecting... Read more
Molecular Diagnostics
view channel
Blood Proteins Could Warn of Cancer Seven Years before Diagnosis
Two studies have identified proteins in the blood that could potentially alert individuals to the presence of cancer more than seven years before the disease is clinically diagnosed. Researchers found... Read more (1)_1.jpg "Image: Ultrasound image of micro-histotripsy liberation of biomarkers in a tumor (Photo courtesy of Joy Wang and Pradyumna Kedarisetti)"){kind=small}
Ultrasound-Aided Blood Testing Detects Cancer Biomarkers from Cells
Ultrasound imaging serves as a noninvasive method to locate and monitor cancerous tumors effectively. However, crucial details about the cancer, such as the specific types of cells and genetic mutations... Read more_1.jpg "Image: The innovative method to customize and strengthen DNA origami structure promises breakthroughs in medicine (Photo courtesy of Shutterstock)")
.jpg "Image: The QIAstat-Dx Respiratory Panel Plus has received U.S. FDA clearance (Photo courtesy of QIAGEN)")
Hematology
view channel
Next Generation Instrument Screens for Hemoglobin Disorders in Newborns
Hemoglobinopathies, the most widespread inherited conditions globally, affect about 7% of the population as carriers, with 2.7% of newborns being born with these conditions. The spectrum of clinical manifestations... Read more
First 4-in-1 Nucleic Acid Test for Arbovirus Screening to Reduce Risk of Transfusion-Transmitted Infections
Arboviruses represent an emerging global health threat, exacerbated by climate change and increased international travel that is facilitating their spread across new regions. Chikungunya, dengue, West... Read more
POC Finger-Prick Blood Test Determines Risk of Neutropenic Sepsis in Patients Undergoing Chemotherapy
Neutropenia, a decrease in neutrophils (a type of white blood cell crucial for fighting infections), is a frequent side effect of certain cancer treatments. This condition elevates the risk of infections,... Read more
First Affordable and Rapid Test for Beta Thalassemia Demonstrates 99% Diagnostic Accuracy
Hemoglobin disorders rank as some of the most prevalent monogenic diseases globally. Among various hemoglobin disorders, beta thalassemia, a hereditary blood disorder, affects about 1.5% of the world's... Read moreImmunology
view channel.jpg "Image: The AI predictive model identifies the most potent cancer killing immune cells for use in immunotherapies (Photo courtesy of Shutterstock)")
AI Predicts Tumor-Killing Cells with High Accuracy
Cellular immunotherapy involves extracting immune cells from a patient's tumor, potentially enhancing their cancer-fighting capabilities through engineering, and then expanding and reintroducing them into the body.... Read more
Diagnostic Blood Test for Cellular Rejection after Organ Transplant Could Replace Surgical Biopsies
Transplanted organs constantly face the risk of being rejected by the recipient's immune system which differentiates self from non-self using T cells and B cells. T cells are commonly associated with acute... Read more
AI Tool Precisely Matches Cancer Drugs to Patients Using Information from Each Tumor Cell
Current strategies for matching cancer patients with specific treatments often depend on bulk sequencing of tumor DNA and RNA, which provides an average profile from all cells within a tumor sample.... Read more
Genetic Testing Combined With Personalized Drug Screening On Tumor Samples to Revolutionize Cancer Treatment
Cancer treatment typically adheres to a standard of care—established, statistically validated regimens that are effective for the majority of patients. However, the disease’s inherent variability means... Read moreMicrobiology
view channel
Integrated Solution Ushers New Era of Automated Tuberculosis Testing
Tuberculosis (TB) is responsible for 1.3 million deaths every year, positioning it as one of the top killers globally due to a single infectious agent. In 2022, around 10.6 million people were diagnosed... Read more
Automated Sepsis Test System Enables Rapid Diagnosis for Patients with Severe Bloodstream Infections
Sepsis affects up to 50 million people globally each year, with bacteraemia, formerly known as blood poisoning, being a major cause. In the United States alone, approximately two million individuals are... Read more
Enhanced Rapid Syndromic Molecular Diagnostic Solution Detects Broad Range of Infectious Diseases
GenMark Diagnostics (Carlsbad, CA, USA), a member of the Roche Group (Basel, Switzerland), has rebranded its ePlex® system as the cobas eplex system. This rebranding under the globally renowned cobas name... Read more
Clinical Decision Support Software a Game-Changer in Antimicrobial Resistance Battle
Antimicrobial resistance (AMR) is a serious global public health concern that claims millions of lives every year. It primarily results from the inappropriate and excessive use of antibiotics, which reduces... Read morePathology
view channel
AI Integrated With Optical Imaging Technology Enables Rapid Intraoperative Diagnosis
Rapid and accurate intraoperative diagnosis is essential for tumor surgery as it guides surgical decisions with precision. Traditional intraoperative assessments, such as frozen sections based on H&E... Read more
HPV Self-Collection Solution Improves Access to Cervical Cancer Testing
Annually, over 604,000 women across the world are diagnosed with cervical cancer, and about 342,000 die from this disease, which is preventable and primarily caused by the Human Papillomavirus (HPV).... Read more
Hyperspectral Dark-Field Microscopy Enables Rapid and Accurate Identification of Cancerous Tissues
Breast cancer remains a major cause of cancer-related mortality among women. Breast-conserving surgery (BCS), also known as lumpectomy, is the removal of the cancerous lump and a small margin of surrounding tissue.... Read more
Technology
view channel
New Diagnostic System Achieves PCR Testing Accuracy
While PCR tests are the gold standard of accuracy for virology testing, they come with limitations such as complexity, the need for skilled lab operators, and longer result times. They also require complex... Read more
DNA Biosensor Enables Early Diagnosis of Cervical Cancer
Molybdenum disulfide (MoS2), recognized for its potential to form two-dimensional nanosheets like graphene, is a material that's increasingly catching the eye of the scientific community.... Read more
Self-Heating Microfluidic Devices Can Detect Diseases in Tiny Blood or Fluid Samples
Microfluidics, which are miniature devices that control the flow of liquids and facilitate chemical reactions, play a key role in disease detection from small samples of blood or other fluids.... Read more
Breakthrough in Diagnostic Technology Could Make On-The-Spot Testing Widely Accessible
Home testing gained significant importance during the COVID-19 pandemic, yet the availability of rapid tests is limited, and most of them can only drive one liquid across the strip, leading to continued... Read moreIndustry
view channel
Danaher and Johns Hopkins University Collaborate to Improve Neurological Diagnosis
Unlike severe traumatic brain injury (TBI), mild TBI often does not show clear correlations with abnormalities detected through head computed tomography (CT) scans. Consequently, there is a pressing need... Read more
Beckman Coulter and MeMed Expand Host Immune Response Diagnostics Partnership
Beckman Coulter Diagnostics (Brea, CA, USA) and MeMed BV (Haifa, Israel) have expanded their host immune response diagnostics partnership. Beckman Coulter is now an authorized distributor of the MeMed... Read more_1.jpg "Image: Thermo Fisher will distribute Bio-Techne products across Europe (Photo courtesy of 123RF)")
