Nicola Royle

Department of Genetics

Somatic and germline instability of human telomeres

 Telomeres are essential components of linear chromosomes and in all vertebrates they are composed of repetitive DNA sequences, based on the (TTAGGG) repeat, that is bound to a protein complex known as Shelterin.  Telomeres are needed to cap chromosomes and it is well known that disruption of telomere function can lead to genome instability that contributes to cancer initiation in some settings. Telomeres are also essential for counter-acting sequence loss that occurs when chromosomes are replicated during each cell division. This is achieved via the enzyme telomerase that has two essential components, an RNA molecule (encoded by TERC) and a protein with reverse transcriptase activity (encoded by TERT). However, in humans telomerase activity is suppressed in differentiated somatic cells and so telomere length decreases, triggering cellular senescence and so contributing to the ageing process.

In addition to the gradual attrition of telomeric DNA other processes also affect telomere length and function, and we are interested in identifying and characterising cellular mechanisms that are involved in the germ-line or somatic cells. For example, we are investigating the role that DNA mismatch repair plays in faithful replication and repair of telomeric DNA and what impact this may have on cellular senescence and cancer. We are also investigating the interaction between epigenetic modifications to telomeric and subtelomeric chromatin and telomere length dynamics in normal somatic cells, cells that express telomerase and cells that use the Alternative Lengthening of Telomeres (ALT) mechanism. In conjunction with Dr Sue Shackleton (Biochemistry) we are looking at telomere molecular biology in cell lines derived from patients with a premature ageing disorder that arises from mutations in the LMNA gene, which encodes a major component of the nuclear lamina. Recently we have also begun to investigate integration of the Human Herpes Virus 6 (HHV6) into telomeric regions of human chromosomes. Approximately 1% of the human population carry an integrated copy of HHV6 but little is known about the mechanism of integration or the impact, if any, that the 160-kb viral genome has on the molecular biology of the adjacent telomere. 

 

For more information about Nicola Royle follow this link.    Nicola Royle is also an affiliate of the Cancer Theme, which is encompassed within the CRUK Leicester Centre.

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College of Life Sciences
University of Leicester
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