Date of Award
Campus Access Thesis
DNA double strand breaks (DSBs) are very deleterious events that occur in cells. Causes can include endogenous agents such as reactive oxygen and nitrogen species, exogenous agents such as ionizing radiation and ultraviolet light, or other sources such as processing of spontaneous DNA lesions or collapse of stalled replication forks. The RecQ helicases are a family of helicases known to aid in the repair of these DSBs and help maintain genomic stability and integrity. WRN and BLM are helicases in the RecQ helicase family. Mutations in the genes for each helicase result in a severe genetic disease. Werner syndrome is caused by a mutation in the WRN gene. Patients with this disease show signs of premature aging and are predisposed to mesenchymal cancers. Bloom's syndrome is caused by a mutation in the BLM gene. Patients with this disease obtain rashes after sun exposure and are predisposed to all cancer types. Previous literature has shown that these two helicases do play a role in genome maintenance. However, specific roles in DSB repair are still unclear. This study focuses on WRN's role in nonhomologous end-joining (NHEJ) and BLM's role in both NHEJ and homologous recombination (HR). This study is unique in that DNA repair substrates were integrated into the genome, which were later used to induce a DSB in the cell. DSB repair events were recovered and analyzed using various methods. It was found that WRN-null cells can repair DSBs by NHEJ where only small deletions or insertions were recoverable. However, many of the clones experienced gross chromosomal rearrangements. BLM-null cells were found to repair DSBs mainly by HR, with many clones yielding crossover events. These abnormalities in DSB repair suggest that both WRN and BLM do have specific roles in DSB repair.
Smith, K. L.(2011). Effect of Werner and Bloom Helicase Deficiencies On Dna Double-Strand Break Repair. (Master's thesis). Retrieved from https://scholarcommons.sc.edu/etd/519