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Project information
Mechanics and execution of homologous recombination - biophysics to the organism

Project Identification
206292/E/17/Z
Project Period
6/2018 - 12/2023
Investor / Pogramme / Project type
Wellcome Trust
  • Wellcome Trust Projects
MU Faculty or unit
Faculty of Medicine
Cooperating Organization
Columbia University
  • Responsible person Prof. Eric Greene
Imperial College London
  • Responsible person Prof. David Rueda
The Francis Crick Institute Limited
  • Responsible person Dr. Simon Boulton

Homologous recombination (HR) is an essential mechanism for the repair of DNA double-strand breaks and damaged replication forks and is associated with genetic disorders, cancer and aging. HR repairs DNA damage by copying the correct genetic information from an intact chromosomal template, which is critically dependent on the recombinase RAD51. To ensure its timely and accurate completion, HR is positively and negatively regulated by RAD51 co-factors and antiPage recombinases. How these HR regulators function at the molecular level remains poorly understood and represents a significant challenge to the field due to the lack of mechanistic resolution afforded by conventional bulk biochemical approaches. We recently pioneered several cutting-edge biophysical approaches to interrogate the HR reaction in unprecedented detail.
Importantly, we demonstrated the power of integrating data from these complementary methodologies to uncover the mechanism of action of the Rad51 paralogs in modulating RAD51 to promote HR. The aim of our proposal is to extend this paradigm to study multiple different HR regulators to gain insights into how they work individually and how they act cooperatively during HR. Deciphering how HR regulators work will provide an improved understanding of the molecular mechanisms relevant to carcinogenesis and may present unique opportunities for therapeutic intervention.

Sustainable Development Goals

Masaryk University is committed to the UN Sustainable Development Goals, which aim to improve the conditions and quality of life on our planet by 2030.

Sustainable Development Goal No. 3 – Good health and well-being

Publications

Total number of publications: 13

2024

2023

2022

2021

2020

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