Structure-Forming CAG/CTG Repeat Sequences are Sensitive to Breakage in the Absence of Mrc1 Checkpoint Function and S-Phase Checkpoint Signaling: Implications for Trinucleotide Repeat Expansion Diseases

• DOI: 10.4161/cc.3.11.1246
• Publication Date: 2011-01-21T19:12:53Z
• Authors: Catherine H. Freu...; Mayurika Lahiri
• Keywords: Okazaki fragments; Checkpoint Kinase 2

Expansion of trinucleotide repeat sequences is the cause multiple inherited human genetic diseases including Huntington's disease and myotonic dystrophy. CTG CAG repeats have been shown to form stable secondary structures that can impair Okazaki fragment processing may impede replication fork progression. We recently showed mutation DNA damage checkpoint proteins results in increased chromosome breaks at expanded CAG/CTG instability (expansions contractions).(1) Here we report long approximately 155 tracts are especially sensitive absence Mrc1 (Claspin) function, implicating S-phase maintenance other secondary-structure forming sequences. Based on all our results, propose a model for detection different types by signaling pathways.