Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:


Novel Role of DNA Repair Protein Linked to Cancer Uncovered

Tufts University researchers in the School of Arts and Sciences have pinpointed a key cellular protein that repairs damaged DNA molecules but may also promote the development of cancer.

Assistant Professor of Biology Mitch McVey and his research team report that DNA polymerase theta, or PolQ, promotes an inaccurate repair process, which can ultimately cause mutations, cell death or cancer. The research is published in the July 1 edition of the open-access journal PLoS Genetics.

"Although scientists have known for several years that the PolQ protein is somehow related to the development of cancer, its exact cellular role has been difficult to pin down," says McVey."Our finding that it acts during inaccurate DNA repair could have implications for biologists who study genomic changes associated with cancer."

DNA is a double stranded molecule shaped like a spiral staircase. Its two strands are linked together by nucleotides -- guanine, cytosine, adenine and thymine -- that naturally complement one another. Under normal conditions, a guanine matches with a cytosine, and an adenine with a thymine.

How DNA Double-Strand Breaks Are Repaired

But during the course of a cell's life, the staircase can become severed into two molecules. These breaks must be repaired if the cells are to accurately replicate and pass on their genetic material. Most breaks are quickly and accurately fixed during the process of homologous recombination (HR), which uses an intact copy of DNA as a template for repair.

However, there is a second, error-prone process called end-joining repair. Here, the broken, double-stranded ends are stitched back together without regard to the original sequence. The ends of the broken strands may be altered by removal or addition of small DNA segments, which can change the genomic architecture.

In a previous paper, McVey and doctoral student Amy Marie Yu were able to demonstrate an alternative form of end-joining by studying how repair proceeds in the absence of DNA ligase 4, an important protein that links together two broken DNA ends.

After analyzing hundreds of inaccurately repaired breaks in the fruit fly Drosophila melanogaster the scientists observed two things. One, extra nucleotides were often inserted into the DNA strands at the point of the break. Second, the insertions were closely related to the original DNA sequences directly adjacent to the break.

Polymerase Theta's Role in DNA Repair and Cancer

In the current PLoS Genetics paper, McVey, Yu and undergraduate Sze Ham Chan showed that polymerase theta plays a dominant role in this alternative repair process. First, it reads the genetic material in DNA adjacent to the break and makes a copy of it. The newly copied DNA can then be used as a molecular splint that holds the broken ends together until they can be permanently joined. In addition, the scientists speculated that the PolQ protein also has the ability to unwind DNA sequences near a break, thereby facilitating alternative end joining.

Other research groups have previously shown that levels of the PolQ protein are higher in several types of human tumors. McVey and his team are currently working to determine if a PolQ-dependent type of alternative end-joining is involved in the development of cancer in people. If this is indeed the case, the PolQ protein could represent a novel target for the development of new cancer drugs.

"Our first goal is to determine which parts of PolQ are required for its role in alternative end- joining," McVey says. "This will give us a road map for determining how its activity might be altered in a clinical setting."

This work was funded by grants from the National Science Foundation and the Ellison Medical Foundation.

Chan SH, Yu AM, McVey M (2010) "Dual Roles for DNA Polymerase Theta in Alternative End- Joining Repair of Double-Strand Breaks in Drosophila."

PLoS Genet 6(7): e1001005. doi:10.1371/journal.pgen.1001005

Tufts University, located on three Massachusetts campuses in Boston, Medford/Somerville, and Grafton, and in Talloires, France, is recognized among the premier research universities in the United States. Tufts enjoys a global reputation for academic excellence and for the preparation of students as leaders in a wide range of professions. A growing number of innovative teaching and research initiatives span all Tufts campuses, and collaboration among the faculty and students in the undergraduate, graduate and professional programs across the university's schools is widely encouraged.

Alex Reid | Newswise Science News
Further information:

More articles from Life Sciences:

nachricht ‘Farming’ bacteria to boost growth in the oceans
24.10.2016 | Max-Planck-Institut für marine Mikrobiologie

nachricht Calcium Induces Chronic Lung Infections
24.10.2016 | Universität Basel

All articles from Life Sciences >>>

The most recent press releases about innovation >>>

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

Im Focus: Light-driven atomic rotations excite magnetic waves

Terahertz excitation of selected crystal vibrations leads to an effective magnetic field that drives coherent spin motion

Controlling functional properties by light is one of the grand goals in modern condensed matter physics and materials science. A new study now demonstrates how...

Im Focus: New 3-D wiring technique brings scalable quantum computers closer to reality

Researchers from the Institute for Quantum Computing (IQC) at the University of Waterloo led the development of a new extensible wiring technique capable of controlling superconducting quantum bits, representing a significant step towards to the realization of a scalable quantum computer.

"The quantum socket is a wiring method that uses three-dimensional wires based on spring-loaded pins to address individual qubits," said Jeremy Béjanin, a PhD...

Im Focus: Scientists develop a semiconductor nanocomposite material that moves in response to light

In a paper in Scientific Reports, a research team at Worcester Polytechnic Institute describes a novel light-activated phenomenon that could become the basis for applications as diverse as microscopic robotic grippers and more efficient solar cells.

A research team at Worcester Polytechnic Institute (WPI) has developed a revolutionary, light-activated semiconductor nanocomposite material that can be used...

Im Focus: Diamonds aren't forever: Sandia, Harvard team create first quantum computer bridge

By forcefully embedding two silicon atoms in a diamond matrix, Sandia researchers have demonstrated for the first time on a single chip all the components needed to create a quantum bridge to link quantum computers together.

"People have already built small quantum computers," says Sandia researcher Ryan Camacho. "Maybe the first useful one won't be a single giant quantum computer...

Im Focus: New Products - Highlights of COMPAMED 2016

COMPAMED has become the leading international marketplace for suppliers of medical manufacturing. The trade fair, which takes place every November and is co-located to MEDICA in Dusseldorf, has been steadily growing over the past years and shows that medical technology remains a rapidly growing market.

In 2016, the joint pavilion by the IVAM Microtechnology Network, the Product Market “High-tech for Medical Devices”, will be located in Hall 8a again and will...

All Focus news of the innovation-report >>>



Event News

#IC2S2: When Social Science meets Computer Science - GESIS will host the IC2S2 conference 2017

14.10.2016 | Event News

Agricultural Trade Developments and Potentials in Central Asia and the South Caucasus

14.10.2016 | Event News

World Health Summit – Day Three: A Call to Action

12.10.2016 | Event News

Latest News

Oasis of life in the ice-covered central Arctic

24.10.2016 | Earth Sciences

‘Farming’ bacteria to boost growth in the oceans

24.10.2016 | Life Sciences

Light-driven atomic rotations excite magnetic waves

24.10.2016 | Physics and Astronomy

More VideoLinks >>>