Fig. 6.
Proposed relationship between the TOP1-TDP1-SSBR and the TC-NER pathways. The TOP1-DNA irreversible cleavage complexes (TOP1icc) that arise normally in the course of TOP1 action are usually taken care of by TDP1 and SSBR, which prevent the formation of the large CAG contractions our system is able to detect. When the TDP1-SSBR pathway is compromised, however, RNA polymerase II stalls at the damage, eliciting involvement of TC-NER, which promotes CAG repeat contractions, as described previously (28, 32).