skip to primary navigationskip to content

Svetlana Khoronenkova

DNA repair and neurodegenerative diseases

Human cells repair thousands of DNA lesions daily. The majority of lesions arise from the intrinsic chemical instability of DNA and include single-strand breaks and base modifications. Unrepaired lesions can obstruct DNA replication, leading to mutations and toxic DNA double-strand breaks. In non-proliferating cells (for example, post-mitotic neurons) damaged DNA bases and single-strand breaks can block transcription, leading to cell death and disease. In particular, defects in DNA repair are often linked to progressive neurological disorders, although their precise roles in the neurological phenotypes remain elusive.

To expand our understanding of the links between deficiencies in the DNA damage response and the molecular nature of neurological diseases, we use in vitro systems reconstituted with purified proteins, mammalian cell culture models and human induced pluripotent stem cells (iPSCs). Biochemical and molecular biological techniques that we use include CRISPR, ChIP, real-time PCR, confocal microscopy, mass spectrometry etc.

This work is supported by the Royal Society and the Wellcome Trust.

Lab members: Brian Ortmann, Stéphanie Rosciglione, Chris Weekes

Key publications:

  • Khoronenkova SV & Dianov GL (2015) ATM prevents DSB formation by coordinating SSB repair and cell cycle progression. Proc. Natl. Acad. Sci. 112, 3997-4002.
  • Khoronenkova SV & Dianov GL (2013) USP7S-dependent inactivation of Mule regulates DNA damage signaling and repair. Nucl. Acids Res. 41, 1750-1756.
  • Khoronenkova SV, Dianova II, Edelmann MJ, Kessler BM, Parsons JL, & Dianov GL (2012) ATM-dependent down-regulation of USP7/HAUSP by PPM1G activates p53 response to DNA damage. Mol. Cell 45, 801-813.

Recruitment: there are currently no funded openings but please contact me if you feel you might be competitive in securing a PhD or post-doctoral fellowship.


Contact details:

Dr Svetlana Khoronenkova
Department of Biochemistry
University of Cambridge
Sanger Building
80 Tennis Court Road
Cambridge CB2 1GA, UK
Tel: +44(0)1223 761449