Cancer research unlocks 30-year genetic puzzle

June 12, 2012

(Medical Xpress) -- Scientists at the University of Sussex have solved a 30-year genetic puzzle that could help enhance treatment for certain types of “inherited” cancers.

The findings relate to an enzyme that plays an important role in the repair of DNA – the genetic blueprint for all life which in mutated form leads to the uncontrolled reproduction of cells and the development of cancers.

The enzyme – PARP1 – was first identified as a DNA damage sensor by Professor Sydney Shall in research undertaken at Sussex in the 1980s. Its discovery led to the development of drugs that blocked the DNA repair mechanism in breast, prostate and ovarian cancers found in people who have a family history of those diseases.

But for the past three decades scientists have not known exactly how the enzyme recognised and repaired DNA damage.

The Cancer Research UK-funded study by the Genome Damage and Stability Centre at Sussex and  the Adolf Butenandt Institute, University of Munich has now shown, using structural biology, biochemistry and cell imaging techniques, that two PARP1 cooperate with each other to detect the damage and then signal to other molecules to bind together at the damage site.

The team’s findings are published online (10 June 2012)  in Nature Structural and Molecular Biology.

The team, led by Professor Laurence Pearl and Dr Antony Oliver have now discovered that molecules within the enzyme, known as PARP1, cooperate to identify DNA damage and then signal to other molecules to bind together and repair the damage on site.

Professor Laurence Pearl, who is head of Life Sciences at the University of Sussex and who led the research with Dr Antony Oliver, says: “When the PARP1 molecules bind together at the site of DNA damage, they cooperate to generate a large molecular ‘flag’ called polyADP-ribose, that signals to other molecules in the cell to come and repair the broken DNA.

“Drugs that stop PARP1 from signaling kill a range of breast, ovarian and prostate cancers in people whose tumours have defects in other DNA systems, and who often come from families with a strong genetic predisposition to those diseases. Now we have a clearer idea of how PARP1 actually recognises damaged DNA and fires off its DNA damage signal, we can target this system with far greater precision.”

The detailed knowledge of how PARP1 signals DNA damage will greatly assist the development of the next generation of drugs that exploit the changes that cause cancers, to kill them, while sparing normal tissues and causing far fewer side effects.

Explore further: Scientists identify protein that improves DNA repair under stress

More information: … .do?structureId=4AV1

Related Stories

Scientists identify protein that improves DNA repair under stress

June 16, 2011
Cells in the human body are constantly being exposed to stress from environmental chemicals or errors in routine cellular processes. While stress can cause damage, it can also provide the stimulus for undoing the damage. ...

New study unravels mystery of a DNA repair process

March 14, 2012
(Medical Xpress) -- Scientists at the University of Sussex have uncovered the mechanism of a key process in DNA repair that helps prevent neurodegenerative diseases such as ataxia.

First evidence of new 'druggable' DNA repair target to destroy cancer cells

November 7, 2011
(Medical Xpress) -- Blocking a key DNA damage repair enzyme, called APE1, could provide a new way to kill cancer cells containing faulty BRCA genes, according to research presented at the National Cancer Research Institute ...

Bacteria shed light on new drug targets for inherited cancers

September 6, 2011
Cancer Research UK scientists have succeeded in purifying a protein found in bacteria that could reveal new drug targets for inherited breast and ovarian cancers - and other cancers linked to DNA repair faults. The study ...

Recommended for you

Study uncovers potential 'silver bullet' for preventing and treating colon cancer

July 26, 2017
In preclinical experiments, researchers at VCU Massey Cancer Center have uncovered a new way in which colon cancer develops, as well as a potential "silver bullet" for preventing and treating it. The findings may extend to ...

Compound shows promise in treating melanoma

July 26, 2017
While past attempts to treat melanoma failed to meet expectations, an international team of researchers are hopeful that a compound they tested on both mice and on human cells in a petri dish takes a positive step toward ...

Understanding cell segregation mechanisms that help prevent cancer spread

July 26, 2017
Scientists have uncovered how cells are kept in the right place as the body develops, which may shed light on what causes invasive cancer cells to migrate.

Study may explain failure of retinoic acid trials against breast cancer

July 25, 2017
Estrogen-positive breast cancers are often treated with anti-estrogen therapies. But about half of these cancers contain a subpopulation of cells marked by the protein cytokeratin 5 (CK5), which resists treatment—and breast ...

Breaking the genetic resistance of lung cancer and melanoma

July 25, 2017
Researchers from Monash University and the Memorial Sloan Kettering Cancer Center (MSKCC, New York) have discovered why some cancers – particularly lung cancer and melanoma – are able to quickly develop deadly resistance ...

Physical activity could combat fatigue, cognitive decline in cancer survivors

July 25, 2017
A new study indicates that cancer patients and survivors have a ready weapon against fatigue and "chemo brain": a brisk walk.


Please sign in to add a comment. Registration is free, and takes less than a minute. Read more

Click here to reset your password.
Sign in to get notified via email when new comments are made.