DNA repair and the CRISPR system

Group leader: Malcolm White

Professor

Research overview

DNA Repair Proteins and Pathways

All organisms invest considerable resources in the maintenance and repair of their genetic material, DNA. This is unsurprising, as the consequences of DNA damage can be mutation, cell death and, in humans, cancer. The archaea are a group of micro-organisms often found in extreme environments. Although they resemble bacteria in most respects, they have key similarities to eukaryotes, including humans, in the way that they process information including their DNA replication and repair pathways. This unexpected relationship makes the archaea an attractive model for the study of DNA repair pathways that are very complex in humans. Archaeal proteins tend to be simpler and are often more stable than their human counterparts, making them ideal for structural and biochemical studies. We utilise a variety of interdisciplinary techniques ranging from microbiology and genetics through biochemistry and molecular biology to biophysics and structural biology. In addition to the intrinsic interest in archaeal DNA repair, these thermostable proteins have potential applications in biotechnology, and our studies can shed light on the equivalent pathways for DNA repair in humans. 

The CRISPR system for antiviral defence

CRISPR is a recently discovered antiviral defence system in prokaryotes. Viral DNA incorporated in the host genome is used to generate interfering CRISPR-RNAs that guide CRISPR associated (CAS) proteins to target and degrade invading viral nucleic acid. The CRISPR pathway is complex with many different enzymes involved and several aspects are very poorly understood. We are investigating the molecular mechanisms of the CRISPR system in Sulfolobus solfataricus, which has three different mechanisms to target and degrade viral nucleic acid.

Publications

Peeters, E, Boon, M, Rollie, CJC, Willaert, RG, Voet, M, White, MF, Prangishvili, D, Lavigne, R & Quax, TEF 2017, 'DNA‐Interacting characteristics of the archaeal Rudiviral protein SIRV2_Gp1' Viruses, vol 9, no. 7, 190. DOI: 10.3390/v9070190
Han, W, Li, Y, Deng, L, Feng, M, Peng, W, Hallstrøm, S, Zhang, J, Peng, N, Liang, YX, White, MF & She, Q 2017, 'A type III-B CRISPR–Cas effector complex mediating massive target DNA destruction' Nucleic Acids Research, vol 45, no. 4, pp. 1983-1993. DOI: 10.1093/nar/gkw1274

Overview

Overview header image

Scientists associated with the thirty-two research groups that are affiliated with the Biomedical Sciences Research Complex perform highly innovative, multi-disciplinary research in eleven broad areas of biomedical research, employing state-of-the-art techniques to address key questions at the leading edge of the biomedical and biological sciences. The BSRC is grateful for funding from all funding agencies including the Institutional Strategic Support Fund from the Wellcome Trust.

Follow the links on the left to view individual research groups associated with one or more of the eleven BSRC research areas.

Research areas

Scientists associated with the thirty-two research groups that are affiliated with the Biomedical Sciences Research Complex perform highly innovative, multi-disciplinary research in eleven broad areas of biomedical research, employing state-of-the-art techniques to address key questions at the leading edge of the biomedical and biological sciences.

Follow the links on the left to view individual research groups associated with one or more of the eleven BSRC research areas.

Research by academic schools

Research in the BSRC is conducted by thirty-two independent research groups based in the Schools of Biology, Chemistry, Physics and Astronomy, and Medicine. Follow the links on the left to view groups associated with each school.