Splicing, genome stability and disease: splice like your genome depends on it!
The spliceosome has been implicated in genome maintenance for decades. Recently, a surge in discoveries in cancer has suggested that the oncogenic mechanism of spliceosomal defects may involve defective genome stability. The action of the core spliceosome prevents R-loop accumulation, and regulates the expression of genome stability factors. At the same time, specific spliceosomal components have non-canonical functions in genome maintenance. Here we review these different models, highlighting their discovery in different model systems, and describing their potential impact on human disease states.
KeywordsSplicing DNA damage R-loops Leukemia Cancer
We thank Dr. S.W. Minaker for critically reading the manuscript. A.S.T. is an Elizabeth C. Watters Scholarship holder. Work on splicing by P.C.S. is supported by a Canadian Institutes of Health Research grant (MOP-136982) and a Rare Diseases Models and Mechanisms (RDMM) Network catalyst grant. We apologize to any authors we did not cite due to lack of space.
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