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When DNA becomes its own enemy

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Video: Our animation explains cell division and DNA replication and how mistakes can cause cancer.

Dr Gideon Coster joined the ICR in October 2018, to set up a new team looking into DNA replication. His research is helping increase our understanding of how DNA is copied when cells divide and how this goes wrong in cancer cells – with the aim of discovering new targets for cancer drugs.

When a cell divides it has to make a copy of everything within it, including its DNA. This means that each of the two new daughter cells have the exact same DNA as the parent cell. This process is called DNA replication.

Dr Coster’s research focuses on how this process works in so-called ‘repetitive DNA sequences’, in which the DNA code is repeated many times over. These sequences make up around half the human genome and they are more difficult to replicate than other regions of our DNA.

What are repetitive DNA sequences?

Dr Coster’s team will be specifically looking at regions of our genome which have repetitive sequences.

  • The building blocks of our DNA are called nucleotides. There are four different DNA nucleotides, represented by the letters: A, T, C, G.
  • Repetitive sequences refer to regions of DNA that follow a particular pattern over and over again, or have one of the nucleotides multiple times, e.g. ACG ACG ACG ACG.
  • DNA is normally present in our cells in a specific structure called the double helix. But research has revealed that DNA can also adopt other 3D structures.
  • We believe that repetitive DNA can fold onto itself into such unusual structures, and that these structures interfere with normal DNA replication. Yet we know remarkably little about these events which occur as cells copy these difficult regions of the genome.

If we can unravel the mechanisms that dictate how DNA correctly duplicates in these more complex repetitive sequences, we can then understand how this duplication goes wrong in cancer.

With your support today, Dr Coster will be able to better understand the fundamental biology of our cells and contribute to improved diagnosis and prognosis for many different types of cancer. The work may also lead him to find new approaches to treating cancer altogether.

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Video: Dr Gideon Coster talks about his team's work on DNA replication and how you can donate to our DNA appeal.

Understanding of DNA repair is benefiting ovarian cancer patients

Anne Goward, aged 54 from Canvey Island, was diagnosed with stage 3c ovarian cancer in June 2015.

She initially had surgery alongside chemotherapy. But then her cancer recurred in January 2017 – and chemotherapy was no longer working for her.

Genetic testing showed she had the BRCA1 gene mutation and so she was able to be treated with a drug called Olaparib.

The development of Olaparib was underpinned by research at the ICR. Olaparib is a PARP inhibitor and it inhibits a particular enzyme (protein) involved in DNA repair.

Anne’s story shows how improving our understanding of fundamental principles can make a huge difference to cancer patients’ lives. We hope Dr Coster’s research could lead to further advances for patients with other types of cancer, including bowel cancer.

“Olaparib has given me hope. I plan to make my son’s 21st birthday and I am even planning holidays! Before, I didn’t think into the future. I’m hopeful that I will have a few years chemo free and feeling good, with fewer side effects.” - Anne Goward