The duplication of DNA requiresthat all the linkages between the two strands of the double helix are removed.To achieve this, all cells express topoisomerases which act around theelongating replication fork to ensure linkage removal is kept in balance withduplex unwinding. Any disruption of linkage removal leads to an accumulation ofDNA topological stress in the DNA which will rapidly arrest fork progression,potentially leading to DNA damage. In the seminar I will discuss my lab’sstudies in the budding yeast Saccharomyces cerevisiae investigating how thereplication fork responds to accumulated DNA topological stress and where inthe genome DNA topological stress disrupts replication dynamics, causing DNAdamage. In particular, I will focus on the key role of the evolutionarilyconserved replication protein Timeless/Swi1/Tof1 in preventing DNA replicationstress at the role and it’s specific role in minimizing the accumulation of DNAtopological stress ahead of the elongating replication fork.