Breaking News
October 19, 2018 - A new approach identified to control Zika virus, dengue fever
October 19, 2018 - Head Blows Without Concussion May Not Damage Brain, Study Claims
October 19, 2018 - US opioid use not declined, despite focus on abuse and awareness of risk
October 19, 2018 - Next-generation RNA sequencing technology sheds new light on human mitochondrial diseases
October 19, 2018 - UT Southwestern biochemist receives 2019 Breakthrough Prize in Life Sciences for innate immunity discovery
October 19, 2018 - The immune system also plays a key role in day-to-day function of healthy organs
October 19, 2018 - New tool may reveal how the brain structure impacts brain activity, human behavior
October 19, 2018 - Trump Administration announces ‘Winning on Reducing Food Waste’ initiative
October 19, 2018 - For-profit nursing home residents more likely to experience health issues caused by substandard care
October 19, 2018 - Conceptual framework proposed to examine role of exercise in multiple sclerosis
October 19, 2018 - Near infrared spectroscopy technique for accurate evaluation of chondral injuries
October 19, 2018 - Scientists receive $5.1 million grant to develop stem cell-based therapy for blinding retinal conditions
October 19, 2018 - Shorter physician encounters associated with antibiotic prescribing
October 19, 2018 - In the Spotlight: Enjoying research and exploring opportunities
October 19, 2018 - Physical activity lowers cardiovascular mortality risk in frail older adults
October 19, 2018 - New imaging tool helps visualize how sound-induced vibrations travel through the ear
October 19, 2018 - Key insights into the application, production of bioactive materials
October 19, 2018 - New urea sorbent could speed up the development of wearable artificial kidney
October 19, 2018 - Intensive care patients’ muscles less able to use fats for energy
October 19, 2018 - FDA Advisory Committee Recommends Approval of Dsuvia for the Treatment of Moderate-to-Severe Acute Pain
October 19, 2018 - 48,XXXY syndrome – Genetics Home Reference
October 19, 2018 - Physical exercise improves the elimination of toxic proteins from muscles
October 19, 2018 - How a new system improved wait times for Stanford kidney transplant patients
October 19, 2018 - Nutrition has bigger positive impact on bone mass and strength than exercise
October 19, 2018 - Study finds lack of progress in media representation of nurses over last 20 years
October 19, 2018 - Many people have trouble understanding differences between OCD and OCPD
October 19, 2018 - New family planning app found to be as effective as modern methods
October 19, 2018 - Gastric Banding, Metformin Similar for Improving Glycemia
October 19, 2018 - Physiologist publishes findings on the role of the protein titin in muscle contraction
October 19, 2018 - What digital health companies need to do to succeed
October 19, 2018 - N. Carolina Sees Alarming Spike in Heart Infections Among Opioid Users
October 19, 2018 - Video monitoring of TB therapy works well in urban and rural areas
October 19, 2018 - Determining acid-neutralizing capacity for OTC antacids
October 19, 2018 - Males who spend more time taking care of kids have greater reproductive success
October 18, 2018 - Study to explore bioethics of brain organoids
October 18, 2018 - Environmental conditions may drive development of multiple sclerosis
October 18, 2018 - Genetically modifying zebrafish provides more accurate disease models
October 18, 2018 - Purdue Pharma, Eisai announce positive topline results from Phase 3 study of lemborexant
October 18, 2018 - 5 Strength-Training Mistakes to Avoid
October 18, 2018 - Immune system’s balancing act keeps bowel disease in check
October 18, 2018 - Anti-inflammatory drug effective for treating lymphedema symptoms | News Center
October 18, 2018 - Keeping Your Voice Young
October 18, 2018 - One-time universal screening recommended to tackle increase in hepatitis C
October 18, 2018 - Researchers to develop new stem cell-based strategies for treating vision disorders
October 18, 2018 - Detecting epigenetic signature may help people stay ahead of inflammatory bowel disease
October 18, 2018 - Understanding AFib: Slowing down the dancing heart
October 18, 2018 - Using NMR to Reduce Fraud
October 18, 2018 - New automated model identifies dense breast tissue in mammograms
October 18, 2018 - Mysterious polio-like illness baffles medical experts while frightening parents
October 18, 2018 - Cases of Acute Flaccid Myelitis on the rise across U.S.
October 18, 2018 - Dietary fiber reduces brain inflammation during aging
October 18, 2018 - New tool could help prioritize recovery efforts for the poorest hit by natural disasters
October 18, 2018 - Hundreds of dietary supplements shown to contain unapproved drugs
October 18, 2018 - Active Pharmaceuticals ID’d in >700 Dietary Supplements
October 18, 2018 - Cell death protein also damps inflammation
October 18, 2018 - AI pathology diagnostic tool developed using deep learning technology from Olympus
October 18, 2018 - Health Highlights: Oct. 15, 2018
October 18, 2018 - Largest study of ‘post-treatment controllers’ reveals clues about HIV remission
October 18, 2018 - Bad Blood in Silicon Valley: A conversation with John Carreyrou
October 18, 2018 - ANTRUK’s Annual Lecture sends out message on shortage of funds for antibiotic research
October 18, 2018 - NAM special publication outlines steps to ensure interoperability of health care systems
October 18, 2018 - Novel method uses just a drop of blood to monitor effect of lung cancer therapy
October 18, 2018 - New blood test could spare cancer patients from unnecessary chemotherapy
October 18, 2018 - Training young researchers to work with data volumes arising in the health sector
October 18, 2018 - New Metrohm IC method is reliable and convenient to use for zinc oxide assay
October 18, 2018 - Global AIDS, TB fight needs more money: health fund
October 18, 2018 - Understanding the forces that cause sports concussions
October 18, 2018 - Research points to new target for treating periodontitis
October 18, 2018 - New tool improves assessment of postpartum depression symptoms
October 18, 2018 - From Biopsy to Diagnosis
October 18, 2018 - Sexual harassment and assault linked to worse physical/mental health among midlife women
October 18, 2018 - Stumped by medical school? A Q&A with a learning specialist
October 18, 2018 - Report predicts life expectancy in 2040, Spain comes out on top
October 18, 2018 - Self-lubricating condoms may help raise condom usage
October 18, 2018 - Targeting immune checkpoints in microglia could reduce out-of-control neuroinflammation
October 18, 2018 - Study finds changes in antiepileptic drug metabolism during different trimesters of pregnancy
October 18, 2018 - Autonomic nervous system directly controls stem cell proliferation, study shows
October 18, 2018 - FDA Approves Talzenna (talazoparib) for gBRCAm HER2-Negative Locally Advanced or Metastatic Breast Cancer
October 18, 2018 - Sleeping Beauty technique helps identify genes responsible for NAFLD-associated liver cancer
October 18, 2018 - Many U.S. adults confused about primary care, study shows
Study identifies key role of TLK1 and TLK2 enzymes in DNA replication

Study identifies key role of TLK1 and TLK2 enzymes in DNA replication

image_pdfDownload PDFimage_print

During cell growth, cells copy their DNA through a process called DNA replication. For this process to be accurate, the genetic and epigenetic information must be copied flawlessly. In this regard, researchers led by Travis H. Stracker at the Institute for Research in Biomedicine (IRB Barcelona), in collaboration with Anja Groth’s group at the Biotech Research & Innovation Centre (BRIC), have identified a key role for the TLK1 and TLK2 enzymes in DNA replication.

“We demonstrated that TLK activity is critical to prevent extensive DNA damage and cell death during DNA replication. And in some human cancers, TLK1 and TLK2 correlate with clinical outcome, thus supporting the idea that they may be promising targets for inhibition, explains Travis H. Stracker, head of the Genomic Instability and Cancer Lab.

Published in Science Advances, the study is based on previous studies that pointed to TLK1/2 as potential candidate targets in cancer therapy, and it provides new molecular details on their key functions in cancer cell proliferation.

This collaborative study has used state-of-the-art molecular approaches to analyze DNA replication and DNA damage, as well as the computational analysis of publicly available cancer data from the Cancer Genome Atlas (TCGA) project.

Fueling the faithful duplication of DNA

The scientists have demonstrated that TLK1 and TLK2 activity is crucial for regulating the availability of histones, abundant proteins that protect DNA, provide structure and carry epigenetic information. “When DNA is copied, cells need to provide twice as many histones and deposit them properly in order to maintain genetic and epigenetic information. If there are too few histones, crucial information is lost and DNA damage occurs,” explains Sandra Segura-Bayona, PhD student in the Genomic Instability and Cancer Lab and one of the first authors of the study.

Potential targets for cancer therapy

The researchers examined the status of the TLK1 and TLK2 genes in over 7000 patient samples made publically available by the Cancer Genome Atlas project. They found that these genes are rarely mutated in cancers, thereby suggesting a potentially conserved role. In many cases, the TLK1 and TLK2 genes were duplicated or overexpressed and in several types of cancer, high expression correlated with poor patient outcome.

Although previous studies had proposed that TLK1/2 were potential targets for breast cancer therapy, this study demonstrates that their inhibition could be useful for the treatment of various kinds of cancer and may enhance the activity of several chemotherapeutic agents currently in clinical trials. These enzymes therefore emerge as potential targets for future drug development.

The study also involved the collaboration of Camille Stephan-Otto Attolini, head of the Biostatistics and Bioinformatics Facility at IRB Barcelona. This study was supported by the former Ministry of Economy, Industry and Competiveness (MINECO), now Ministry of Science, Innovation and Universities and by a “la Caixa” PhD fellowship awarded to Sandra Segura-Bayona.

Source:

https://www.irbbarcelona.org/en/news/key-role-identified-for-enzymes-in-dna-replication-and-sensitivity-to-chemotherapeutic-drugs

Tagged with:

About author

Related Articles