Wolfson Institute for Biomedical Research


Andrei L. Okorokov

Chromosome Stability
Andrei L Okorokov Photo

020 7679 0959
Email: a.okorokov@ucl.ac.uk

Our group’s research programme brings together cell, molecular and structural biology of the protein machineries and signalling pathways controlling and maintaining the integrity of our chromosomes. We have three main areas of research interest:

We are exploring how cellular tumour suppressors coordinate DNA metabolism processes. Our research focuses on the p53 protein, a major tumour suppressor activated in response to DNA damage. This protein can induce either cell growth arrest and DNA repair, or cell death. Our recently solved structures of the complete p53 tetramer and p53 in complex with its specific DNA target outlay structure-function relationship principles for this paramount “Guardian of Genome”.

Human SIRT1 is a NAD+-dependent protein deacetylase that belongs to the conserved Sirtuin family. It participates in cellular controls of gene expression, metabolism, genomic stability and anti-ageing. Our recent work demonstrated that human SIRT1 is also an essential contributor to chromosomal condensation during mitosis. Lack of SIRT1 in human cells leads to improper chromosome condensation, chromosome "bridges" and breakage, and aneuploidy, indicating that SIRT1 activity in mitosis is vital for chromosome stability.

The first line of the cells’ defence lies at the very beginning of the DNA replication process. Part of our research is focused on the assembly and function of the human DNA replication protein machinery, in particular the process of DNA replication initiation. We are currently working on the human DNA replication initiation protein MCM10, and are trying to elucidate its structure-function relationship using a multidisciplinary approach.

Academic Career