Julia Sidorova, PhD

Clinical and Research Background

We study “good” and “bad” DNA replication: how normal and cancer cells replicate their DNA and how replication as a whole and individual replication forks resist disruptions. When cells replicate their DNA under suboptimal or abnormal conditions (e.g. with low or unbalanced dNTP pools, or when DNA is damaged), many replication features, including the rate of progression of replication forks and the frequency of origin firing, severely deviate from the norm. As a result of this, a fraction of DNA in the genome may fail to replicate or may develop double strand breaks. This condition, referred to as replication stress, leads to genetic instability and can reduce cellular life span, promote carcinogenesis, and even affect innate immunity and epigenetic memory of cells. Previously, we have studied the roles of the RECQ helicase WRN, mutated in the Werner syndrome of premature aging and cancer predisposition, in cellular resistance to replication stress. Our current interests are focused on how maintenance and transmission of epigenetic marks on histone proteins are affected by replication stress and whether they may also help to counteract it; how oncogenes trigger replication stress, and how constitutive replication stress in cancer cells can be exploited in cancer therapy.