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The Patrick G Johnston Centre for Cancer Research

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  • Genomic instability

Genomic instability

Core technology units banner 1600 575 genomics
Disciplinary strengths
Genomic Instability

Genomic instability, GI, is a term used to describe increased DNA damage. It is well known that accurate replication of DNA is essential to prevent the accumulation of DNA damage and many of the better known cancer genes (e.g. BRCA1) play a role in maintaining accurate DNA replication. Cancer cells often exhibit GI with an increased number of mutations, leading to changes which can drive the development of cancer cells. Unlike simpler organisms such as bacteria, mammalian DNA is packaged into ‘chromatin’ and enzymes involved in this role can also contribute to GI if they become dysregulated. GI can trigger anti-cancer safety mechanisms in the cell such as permanent cell cycle arrest (senescence), or cell death (apoptosis) but cancer cells can often over-ride or 'bypass' such mechanisms. Another important safety mechanism through which cells prevent the development of cancer is through signalling to the immune system. Cells with persistently damaged DNA can alert immune cells, so that they can be selectively targeted and destroyed before they become cancerous.

Our research in the CCRCB brings several of these concepts together in an effort to investigate mechanisms involved in driving GI and cancer growth/spread. These include:

  • The identification of genes involved in the repair of DNA damage, whose downregulation or mutation leads to GI
  • The identification of genes involved in bypassing safety mechanisms (such as senescence and apoptosis), allowing cancer cells to survive in a background of high GI
  • The identification of genes important for accurate chromatin packaging (such as epigenetic enzymes) and how they contribute to GI and cancer
  • Evaluation of the role of innate immune signalling (such as the cGAS/STING pathway) in the eradication of pre-cancerous and cancerous cells with high GI

The ultimate aims of these investigations are to find ways of exploiting novel findings related to GI in cancers and therefore improve the treatment and survival of cancer patients.

Principal Investigator Links

Prof Richard Kennedy Prof Paul Harkin
Dr Paul Mullan Dr Nick Orr
Dr Kienan Savage Dr Simon McDade
Dr Stuart McIntosh  Dr Kostantin Panov
Dr. Adone Mohd-Sarip  

Genomics 800

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The Patrick G Johnston Centre for Cancer Research

Queen's University Belfast
97 Lisburn Road
Belfast
BT9 7AE

Phone: +44 (0) 28 9097 2760
Email: pgjccr@qub.ac.uk  
Fax: +44 (0) 28 9097 2776

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