Abstract 3012: The Snm1B/Apollo DNA nuclease functions in resolution of replication stress and maintenance of genome stability

A critical aspect of normal cellular processes is the maintenance of genomic stability. Defects in cellular responses to DNA damage can lead to an accumulation of unrepaired or misrepaired lesions and ultimately, increased genome instability. Genomic DNA is constantly damaged through exposure to exogenous agents as well as during endogenous processes, including DNA replication. Progression of the replication fork can be impaired by structural or physical blocks leading to fork stalling. If stalled forks are not properly restarted or repaired, they can collapse, leading to chromosomal damage including breaks, deletions, and translocations. Therefore, replication stress associated DNA damage has been hypothesized as one important source of genome instability associated with cancer initiation and progression.Cells have evolved intricate mechanisms to detect, signal, and resolve stalled replication forks; however, the molecular events involved in these fundamental processes have not been fully defined. My studies are focused on the DNA nuclease SNM1B/Apollo which plays critical roles in repairing stalled or blocked replication forks and also in telomere maintenance. We previously reported that SNM1B functions within the Fanconi anemia (FA) pathway, which is required for efficient stabilization of stalled replication forks. Mutations in the 16 known FA genes cause Fanconi anemia, a human genome instability disorder characterized by cancer predisposition, progressive bone marrow fa...
Source: Cancer Research - Category: Cancer & Oncology Authors: Tags: Molecular and Cellular Biology Source Type: research