PRESS-NEWS.org - Press Release Distribution
PRESS RELEASES DISTRIBUTION

A new map reveals the complicated world in which cells seek to repair damaged DNA

A new map reveals the complicated world in which cells seek to repair damaged DNA
2023-05-22
(Press-News.org) Writing in the May 22, 2023 issue of Cell Systems, a diverse team of scientists, led by researchers at University of California San Diego School of Medicine, have produced a novel map that depicts the human body’s enormously complicated and highly evolved system for addressing and repairing DNA damage — a cause and consequence of many diseases.

Damage to DNA and replication errors caused by stress and other factors play a major role in disease, and are a hallmark of cancer and other afflictions. To maintain the integrity of the genome and support normal functioning and health, cells have evolved an intricate network of cell-cycle checkpoints and DNA damage repair tools, collectively known as DNA damage response or DDR. 

Defects in DDR are linked to numerous diseases, including cancer and heritable neurological disorders caused by unstable DNA, erroneous repeats, rearrangements and mutations. Conversely, better understanding how DDR works and why it sometimes fails provides new therapeutic opportunities to treat or cure the same diseases. 

“The ongoing challenge, of course, is that DDR is an extremely complex system involving hundreds of different proteins assembling in different ways to address different problems,” said senior author Trey Ideker, PhD, professor at UC San Diego School of Medicine and UC San Diego Moores Cancer Center. “You can’t fix a problem with DDR until you understand how it works.”

In the new paper, Ideker and colleagues take a major step forward in elucidating the complexities and functions of DDR, producing a multi-scale map of protein assemblies in DDR. 

Unlike earlier maps, based on published scientific literature that included conflicting findings or tend to focus only on well-studied mechanisms, the new reference map employs affinity purification mass spectrometry and a broad collection of multi-omics data to develop a fuller picture: a hierarchical organization of 605 proteins in 109 assemblies that captures canonical repair mechanisms and proposes new DDR-associated proteins linked to stress, transport and chromatin functions within cells. 

Multi-omics is a new approach in which data sets of different omics groups are combined during analysis to create a more complete and nuanced understanding of whole systems and organisms. 

The cell contains different classes of molecular processes: genomics, transcriptomics, proteomics and others. Each of these "omics" molecular processes involves interactions between thousands of genes, transcripts or proteins. To make sense of this complexity, scientists have tended to take a reductionist view, examining omics one at a time. 

In contrast, systems biology considers molecular processes simultaneously and holistically, using machine learning and other tools to evaluate to what extent different molecular processes inform any given interaction, and how whole systems and networks work. Machine learning describes computer systems that are able to learn and adapt without following explicit instructions. It is an application of artificial intelligence.

“Experimental screens of ever-increasing scale are capturing interactions between genes or proteins in human cells, often beyond what has been described in literature. They can, in principle, be used to create data-driven maps of DDR,” said first author Anton Kratz, PhD, formerly a research scientist in Ideker’s lab who now works at The System Biology Institute in Tokyo, Japan. 

But screening presents its own challenges since different forms may measure molecular processes in isolation, missing some interactions that appear only under certain stresses or conditions. To address these challenges, the researchers measured new protein-protein interaction networks centered around 21 key DDR factors with and without DNA damage. They developed a machine learning approach to combine new data with existing data, and statistical analysis that showed the results significantly informed the resulting map.

“To me, two things were most revelatory,” said Kratz. “First, the sheer amount of novel proteins in the map. About 50% of the proteins included in the map following our data-driven paradigm were not included in the literature-curated maps considered here, justifying a data-driven approach to building the map. 

“Second and related to that, membership to DDR is not a binary affair, but takes place on a continuum (and we quantify this continuum), extending to stress, transport, and chromatin functions.”

The researchers have created interactive software that will enable other scientists to investigate proteins and DDR interactions of specific interest. Kratz said scientists can also use the map as a component in visible machine learning systems that potentially could illuminate larger questions, such as how DDR is relevant in the transition from genotype (the genetic constitution of an individual organism) to phenotype (characteristics of an individual resulting from interaction of its genotype with the environment). For example, how drug or toxin exposure might change the DDR. 

Co-authors include: Minkyu Kim, Maya Modak and Nevan J. Krogan, UC San Francisco; Mark Kelly, Fan Zheng, Keiichiro Ono, Yue Qin, Christopher Churas, Jing Chen, Rudolf T. Pillich, Jisoo Park, Rachel Collier, Kate Licon and Dexter Pratt, all at UC San Diego; Christopher A. Koczor, Jianfeng Li, University of South Alabama; Robert W. Sobol, Brown University.

# # #

END

[Attachments] See images for this press release:
A new map reveals the complicated world in which cells seek to repair damaged DNA

ELSE PRESS RELEASES FROM THIS DATE:

What constitutes a paradigm shift? An olive shrub’s mating system as a case study of Kuhn’s theory

2023-05-22
Philosopher Thomas Kuhn’s influential theory of how scientific knowledge is built introduced the term “paradigm shift” to explain a transformation of a field’s ideas and methods. “A Paradigm Shift, or a Paradigm Adjustment? The Evolution of the Oleaceae Mating System as a Small-Scale Kuhnian Case Study,” a new paper published in The Quarterly Review of Biology, seeks to apply this analytical framework to a small controversy in population biology: the mating system of the shrub Phillyrea angustifolia. Traditional theory states that the sex ratio of a population should be 1:1 male to female (or ...

New book eyes Earth's excavators, from microbes to elephants and dinosaurs

New book eyes Earths excavators, from microbes to elephants and dinosaurs
2023-05-22
The ordinary person looks at Georgia’s Stone Mountain and sees a solid, unmovable monolith. Emory University paleontologist Anthony Martin, who thinks in geologic time, sees something more akin to a giant sugar cube. Ever since the crystalized mass of igneous-born minerals rose from deep underground, pushed by the upwelling of magma that formed the Blue Ridge Mountains around 350 million years ago, the giant rock’s flanks have faced continuous assault — and not just from weather and water. Stone Mountain “is fighting a battle against life, and life is winning,” Martin writes ...

Does hydrocortisone improve treatment of septic shock?

2023-05-22
Sepsis is a global health priority affecting 55 million patients worldwide and causing 11 million deaths annually. Treatment for sepsis may include prompt recognition, source control, antibiotics, fluids, vasopressors, and adjunctive therapies. Corticosteroids have been evaluated as adjunctive therapy for septic shock for more than 50 years. Despite this substantive body of research, uncertainty persists about the effects of corticosteroids on mortality. In a study publishing May 22, 2023 in the New England Journal of Medicine: ...

Risk biomarkers could predict serious side effect of stem cell transplant

Risk biomarkers could predict serious side effect of stem cell transplant
2023-05-22
Doctors are one step closer to having a risk biomarker to alert them to which of their pediatric stem cell transplant patients are likely to experience a potentially deadly side effect called sinusoidal obstruction syndrome (SOS). A team led by MUSC Hollings Cancer Center researcher Sophie Paczesny, M.D., Ph.D., published the results of its biomarker study in JCI Insight this month. There is a drug, defibrotide, approved to treat SOS. Paczesny hopes the results of the biomarker study will encourage defibrotide’s manufacturer to conduct a multicenter clinical trial testing ...

First Contact: Global team simulates message from extraterrestrial intelligence to Earth

First Contact: Global team simulates message from extraterrestrial intelligence to Earth
2023-05-22
First Contact: Global team simulates message from extraterrestrial intelligence to Earth A Sign in Space imagines how Earth might respond to a signal from aliens and invites the public to help decode an ET message. May 22, 2023, Mountain View, CA – What would happen if we received a message from an extraterrestrial civilization? Daniela de Paulis, an established interdisciplinary artist and licensed radio operator who currently serves as Artist in Residence at the SETI Institute and the Green Bank Observatory, has brought ...

GPR141 regulates breast cancer progression via oncogenic mediators and the p-mTOR/p53 axis

GPR141 regulates breast cancer progression via oncogenic mediators and the p-mTOR/p53 axis
2023-05-22
“This research uncovers GPR141 as a stimulator of breast tumorigenesis and metastasis, making it a candidate target for breast cancer therapeutics.” BUFFALO, NY- May 22, 2023 – A new research paper was published in Oncotarget's Volume 14 on May 19, 2023, entitled, “G-protein-coupled receptor 141 mediates breast cancer proliferation and metastasis by regulating oncogenic mediators and the p-mTOR/p53 axis.” Breast cancer morbidity is surging towards the peak in females across the globe. An inherent property of cancer cells is enhanced cell proliferation rate and migration capability, leading to deregulated cell ...

Study highlights long-term benefits of family-based care following institutional care

2023-05-22
SAN FRANCISCO, May 22, 2023 – New research, published online today in the American Journal of Psychiatry, provides the most robust and comprehensive evidence to date that children exposed to early psychosocial deprivation benefit substantially from family-based care. Senior author Kathryn L. Humphreys, Ph.D., discussed this work today at a special briefing during the 2023 Annual Meeting of the American Psychiatric Association. Results of research from the Bucharest Early Intervention Project, the ...

Corals mark friendly algae for ingestion—revealing possible conservation target

Corals mark friendly algae for ingestion—revealing possible conservation target
2023-05-22
Baltimore, MD—New research led by Carnegie’s Yixian Zhen and Minjie Hu reveals how coral cells tag friendly algae before ingesting them, initiating a mutually beneficial relationship. This information could guide next-level coral conservation efforts.   Their work is published in Nature Microbiology.  Corals are marine invertebrates that build large exoskeletons from which reefs are constructed. But this architecture is only possible because of a mutually beneficial relationship between the coral and various species of single-celled algae called dinoflagellates ...

WVU researchers see need to strengthen mental health programs for first responders

WVU researchers see need to strengthen mental health programs for first responders
2023-05-22
Controlling traumatic situations is synonymous with the daily duties of first responders, yet many mental health programs to combat the increasing stress they encounter are lacking. That’s why West Virginia University researchers are identifying steps policymakers and community members can take to aid front-line workers. “With elevated risk for suicide and other mental health issues among first responders, we have a significant public health problem,” said Michael Fisher, assistant professor in the WVU School of Public Health ...

Study may explain why high-sugar diets can worsen IBD

Study may explain why high-sugar diets can worsen IBD
2023-05-22
Excess sugar hampers cells that renew the colon’s lining in a mouse model of inflammatory bowel disease (IBD), according to a new study by University of Pittsburgh scientists. The findings, published in Cellular and Molecular Gastroenterology and Hepatology, could help get to the bottom of why limiting sugary foods can ease symptoms for patients with IBD. “The prevalence of IBD is rising around the world, and it’s rising the fastest in cultures with industrialized, urban lifestyles, which typically have diets high in sugar,” said senior author Timothy Hand, Ph.D., associate professor of pediatrics and immunology at Pitt’s ...

LAST 30 PRESS RELEASES:

High-quality nanodiamonds for bioimaging and quantum sensing applications

New clinical practice guideline on the process for diagnosing Alzheimer’s disease or a related form of cognitive impairment or dementia

Evolution of fast-growing fish-eating herring in the Baltic Sea

Cryptographic protocol enables secure data sharing in the floating wind energy sector

Can drinking coffee or tea help prevent head and neck cancer?

Development of a global innovative drug in eye drop form for treating dry age-related macular degeneration

Scientists unlock secrets behind flowering of the king of fruits

Texas A&M researchers illuminate the mysteries of icy ocean worlds

Prosthetic material could help reduce infections from intravenous catheters

Can the heart heal itself? New study says it can

Microscopic discovery in cancer cells could have a big impact

Rice researchers take ‘significant leap forward’ with quantum simulation of molecular electron transfer

Breakthrough new material brings affordable, sustainable future within grasp

How everyday activities inside your home can generate energy

Inequality weakens local governance and public satisfaction, study finds

Uncovering key molecular factors behind malaria’s deadliest strain

UC Davis researchers help decode the cause of aggressive breast cancer in women of color

Researchers discovered replication hubs for human norovirus

SNU researchers develop the world’s most sensitive flexible strain sensor

Tiny, wireless antennas use light to monitor cellular communication

Neutrality has played a pivotal, but under-examined, role in international relations, new research shows

Study reveals right whales live 130 years — or more

Researchers reveal how human eyelashes promote water drainage

Pollinators most vulnerable to rising global temperatures are flies, study shows

DFG to fund eight new research units

Modern AI systems have achieved Turing's vision, but not exactly how he hoped

Quantum walk computing unlocks new potential in quantum science and technology

Construction materials and household items are a part of a long-term carbon sink called the “technosphere”

First demonstration of quantum teleportation over busy Internet cables

Disparities and gaps in breast cancer screening for women ages 40 to 49

[Press-News.org] A new map reveals the complicated world in which cells seek to repair damaged DNA