Lawrence Berkeley National Laboratory
Close encounters: Moving along bumps, breaks, and bubbles on expanded trinucleotide tracts.
- Author(s): Polyzos, Aris A
- McMurray, Cynthia T
- et al.
Published Web Locationhttp://www.sciencedirect.com/science/article/pii/S1568786417302173
Expansion of simple triplet repeats (TNR) underlies more than 30 severe degenerative diseases. There is a good understanding of the major pathways generating an expansion, and the associated polymerases that operate during gap filling synthesis at these "difficult to copy" sequences. However, the mechanism by which a TNR is repaired depends on the type of lesion, the structural features imposed by the lesion, the assembled replication/repair complex, and the polymerase that encounters it. The relationships among these parameters are exceptionally complex and how they direct pathway choice is poorly understood. In this review, we consider the properties of polymerases, and how encounters with GC-rich or abnormal structures might influence polymerase choice and the success of replication and repair. Insights over the last three years have highlighted new mechanisms that provide interesting choices to consider in protecting genome stability.