Mankouri Group – University of Copenhagen

Mankouri Group

Molecular Aging Program
Center for Chromosome Stability
Center for Healthy Aging

Yeast Molecular Aging Team 

Research Interests

“DNA replication stress” is caused by defects in normal replication fork progression and is a major threat to genome stability. It is a commonly observed feature of cancer cells, and also implicated as a driving force for age-associated functional decline in certain cell types. Our primary research interests are to characterise the molecular events that occur following site-specific DNA replication fork perturbation, and determine how these events impact upon general cell physiology and ageing. Much of our research utilizes the model organism, budding yeast, which allows us to combine molecular genetics with the analysis of DNA replication at defined loci. Key findings in yeast will then be directly extrapolated to mammalian systems.

Current Project Areas 

  • To use and develop novel innovative methodologies to detect and characterise site-specific stalled replication forks in vivo.
  • To characterise DNA replication defects occurring in yeast models of human genetic instability disorders (e.g. the yeast sgs1 mutant, which lacks a conserved RecQ helicase that is mutated in the cancer-prone disorder, Bloom’s syndrome).
  • To understand how chromosome instability is counteracted at naturally difficult-to-replicate sites in the genome (e.g. telomeres, and late-replicating sequences).
  • To analyse how under-replicated, or incompletely processed, regions of the genome that are carried-over into mitosis can interfere with subsequent chromosome segregation events. 

Selected publications 

  • Mankouri, H. W., Huttner, D. and Hickson I. D. (2013). How unfinished business from S-phase affects mitosis and beyond. The EMBO Journal 32 (20), 2661-71

  • Larsen, N. B., Sass, E., Suski, S., Mankouri, H. W.* and Hickson I. D.* (2014).  The Escherichia coli Tus-Ter replication fork barrier causes site-specific DNA replication perturbation in yeast. Nature Communications 5:3574 doi: 10.1038/ncomms4574
    (* Co-corresponding authors)

  • Tus-Ter as a tool to study site-specific DNA replication perturbation in eukaryotes. Larsen, N. B., Hickson, I. D. and Mankouri H. W. (2014). Cell Cycle 13 (19), 2994-2998.

  • Larsen, N. B., Liberti, S. E., Vogel, I., Jørgensen, S.W., Hickson, I. D.*  and Mankouri, H. W.* (2017). A stalled replication fork generates a distinct mutational signature in yeast. Proceedings of the National Academy of Sciences 114 (36), 9665-9670.
    (* Co-corresponding authors)