Cancer is a disease of the genome1. The human genome is constantly challenged to repair mistakes caused by internal and external stressors to avoid genetic alterations that may disrupt gene function and perturb normal cell growth2-5. Cells that have acquired the ability for unregulated cell division proliferate indefinitely and acquire additional genetic alterations in the process5. The accumulation of genetic alterations, or genome instability, is a driving force in cancer and, in turn, can contribute to the progressive deterioration of normal cell function2. Although genome instability is a characteristic of almost all human cancers and considered a defining hallmark, the amount and type of genomic instability in tumour genomes differ substantially across tumour types and cell types4,6. Furthermore, the precise source of genome instability can stem from nearly all DNA transactions: replication, transcription, repair, and recombination3. In the last couple decades, an appreciation for the critical role of DNA repair in cancer has slowly become more apparent. It is now widely accepted that cancer cells suppress these mechanisms either to initiate cancer or to continue uncontrollable proliferation.
In my research, I study the role of DNA helicases: essential genes that repair DNA damage and prevent mutations from occurring in the genomes of cells. The gene class, RecQ helicases, have been implicated in aging and cancer due to their association with rapid aging syndromes that are susceptible to cancer. RECQL5 is one gene in this class that has remained understudied for its role in DNA repair. Until recently, studying DNA repair has been limited to molecular methods which suffer from limited resolution and throughput. I used a novel single cell sequencing method, known as Strand-seq, to identify genomic regions prone to DNA repair. I developed novel wet-lab and bioinformatic methods to improve the overall quality of DNA repair studies in single cells using Strand-seq. I found that that specific regions in the genome are troublesome for replication and RecQ helicases have a protective role in the faithful replication of DNA in these areas.