The London Research Institute research groups are based at Lincoln’s Inn Fields and Clare Hall. Our major research themes are: the biology of tumours and tissues, cellular regulatory mechanisms and genomic integrity and cell cycle.
Svend Petersen-Mahrt : DNA Editing
The goal of the DNA Editing Laboratory was to understand the regulatory mechanisms that control the spatial and temporal cellular distribution as well as enzymatic activity of DNA deaminases. This would involve the discovery of proteins that interact with the deaminase, structural DNA elements that influence the specificity of the reaction, as well as chemicals that can inhibit or activate their overall reactivity towards DNA.
DNA instability is considered a hallmark for cellular malignancy. Yet our bodies utilise DNA lesions during the formation of a functional immune system. Furthermore, DNA instability is required during meiosis in gametes. Either process relies on the change of DNA repair from its normal function of faithful DNA stability to one of inaccurate (yet controlled) DNA alterations. The lab identified another physiological molecular mechanism that requires DNA instability – epigenetic reprogramming. Here methylated cytosine bases in DNA (5meC) are modified to an unstable intermediate, with DNA repair resolving the lesion back to a stable, but epigenetically changed cytosine. The lab’s work on AID, a DNA deaminase, has provided a number of new molecular insights on pathways of protein induced DNA demethylation.
Svend left the LRI to join the IFOM-IEO campus in Milan.
Significant LRI Papers
- Pauklin S, Sernández IV, Bachmann G, Ramiro AR, Petersen-Mahrt SK. Estrogen directly activates AID transcription and function. Journal of Experimental Medicine 2009;206:99-111 (Abstract)
- Harris RS, Bishop K N, Sheehy AM, Craig HM, Petersen-Mahrt SK, Watt IN, Neuberger MS and Malim M H. DNA deamination mediates innate immunity to retroviral infection. Cell. 2003;113:803-809 (Abstract)
- Harris RS, Petersen-Mahrt S, Neuberger MS. RNA editing enzyme APOBEC1 and some of its homologues can act as DNA mutators. Molecular Cell. 2002;10:1247-1253 (Abstract)
- Petersen-Mahrt S, Harris RS, Neuberger MS. AID mutates E. coli suggesting a DNA deamination mechanism for antibody diversification. Nature. 2002;418:99-104 (Abstract)