Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

NYU and MSKCC research provides model for understanding chemically induced cancer initiation

10.03.2005


A team from the chemistry and biology departments of New York University, in collaboration with Memorial Sloan Kettering Cancer Center (MSKCC), has uncovered a conformational switch--a change in shape in a carcinogen-damaged DNA site--in tumor suppressor genes altered by a known cancer-causing chemical found in cigarette smoke. This finding may open new horizons for understanding the initiation of chemically induced cancers.



The findings appear as the cover story in the latest issue of the Journal of Molecular Biology. This team was headed by Dinshaw Patel at MSKCC, Nicholas Geacintov, chair of NYU’s chemistry department, and Suse Broyde, a professor in NYU’s biology department.

The studied gene, p53, is an important tumor suppressor gene that plays critical roles in cellular functions such as cell-cycle control, differentiation, and DNA repair. Many different chemical carcinogens, including those that are primary components of cigarette smoke, are known to damage DNA. This damage occurs at special positions of the p53 gene, called mutation hot spots, which have been previously linked with cigarette smoke. This molecular link between chemical DNA damage and cigarette-associated lung cancer has been called the "smoking gun."


In the study, the conformational switch discovered by the research team entails a change in the conformation of a carcinogen-damaged site in a DNA model sequence similar to that in a p53 mutation hot spot. The change is brought about by the presence of a single methyl group (composed only of one carbon and three hydrogen atoms) on a cytosine base adjacent to the damaged site. Without this methyl group, the bulky chemical carcinogen resides at an external binding site in the minor groove of the DNA double helix. However, in the presence of this single methyl group, it assumes an intercalated structure in which the carcinogenic residue is sandwiched between adjacent base pairs in the double helix.

"Such conformational differences in methylated and unmethylated DNA sequences may be significant because of potential alterations in the cellular processing of these lesions by DNA transcription, replication, and repair enzymes," said NYU’s Geacintov.

"Because environmental chemical carcinogens, including those present in cigarette smoke, are a significant threat to human health, it is imperative to understand how chemicals can induce mutations and cancer at the molecular level," added NYU’s Broyde. "Such information is needed for devising novel preventive and therapeutic strategies for addressing the problem of cancer induction by environmental chemical carcinogens."

The researchers added that the finding opens new horizons, at the molecular level, for understanding the effects of methylation at p53 mutation hot spots on the properties of carcinogen-DNA lesions. Current thinking in the field of chemical carcinogenesis is that the mutation-prone, or error-free processing of such carcinogen-damaged p53 genes by DNA repair proteins and DNA and RNA polymerases can determine whether these lesions ultimately contribute to the development of lung and other cancers.

James Devitt | EurekAlert!
Further information:
http://www.nyu.edu

More articles from Life Sciences:

nachricht Staying in Shape
16.08.2018 | Max-Planck-Institut für molekulare Zellbiologie und Genetik

nachricht Chips, light and coding moves the front line in beating bacteria
16.08.2018 | Okinawa Institute of Science and Technology (OIST) Graduate University

All articles from Life Sciences >>>

The most recent press releases about innovation >>>

Die letzten 5 Focus-News des innovations-reports im Überblick:

Im Focus: Unraveling the nature of 'whistlers' from space in the lab

A new study sheds light on how ultralow frequency radio waves and plasmas interact

Scientists at the University of California, Los Angeles present new research on a curious cosmic phenomenon known as "whistlers" -- very low frequency packets...

Im Focus: New interactive machine learning tool makes car designs more aerodynamic

Scientists develop first tool to use machine learning methods to compute flow around interactively designable 3D objects. Tool will be presented at this year’s prestigious SIGGRAPH conference.

When engineers or designers want to test the aerodynamic properties of the newly designed shape of a car, airplane, or other object, they would normally model...

Im Focus: Robots as 'pump attendants': TU Graz develops robot-controlled rapid charging system for e-vehicles

Researchers from TU Graz and their industry partners have unveiled a world first: the prototype of a robot-controlled, high-speed combined charging system (CCS) for electric vehicles that enables series charging of cars in various parking positions.

Global demand for electric vehicles is forecast to rise sharply: by 2025, the number of new vehicle registrations is expected to reach 25 million per year....

Im Focus: The “TRiC” to folding actin

Proteins must be folded correctly to fulfill their molecular functions in cells. Molecular assistants called chaperones help proteins exploit their inbuilt folding potential and reach the correct three-dimensional structure. Researchers at the Max Planck Institute of Biochemistry (MPIB) have demonstrated that actin, the most abundant protein in higher developed cells, does not have the inbuilt potential to fold and instead requires special assistance to fold into its active state. The chaperone TRiC uses a previously undescribed mechanism to perform actin folding. The study was recently published in the journal Cell.

Actin is the most abundant protein in highly developed cells and has diverse functions in processes like cell stabilization, cell division and muscle...

Im Focus: Lining up surprising behaviors of superconductor with one of the world's strongest magnets

Scientists have discovered that the electrical resistance of a copper-oxide compound depends on the magnetic field in a very unusual way -- a finding that could help direct the search for materials that can perfectly conduct electricity at room temperatur

What happens when really powerful magnets--capable of producing magnetic fields nearly two million times stronger than Earth's--are applied to materials that...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

VideoLinks
Industry & Economy
Event News

Within reach of the Universe

08.08.2018 | Event News

A journey through the history of microscopy – new exhibition opens at the MDC

27.07.2018 | Event News

2018 Work Research Conference

25.07.2018 | Event News

 
Latest News

Staying in Shape

16.08.2018 | Life Sciences

Diving robots find Antarctic seas exhale surprising amounts of carbon dioxide in winter

16.08.2018 | Earth Sciences

Protein droplets keep neurons at the ready and immune system in balance

16.08.2018 | Life Sciences

VideoLinks
Science & Research
Overview of more VideoLinks >>>