Proliferating cell nuclear antigen prevents trinucleotide repeat expansions by promoting repeat deletion and hairpin removal.

ABSTRACT: DNA base lesions and base excision repair (BER) within trinucleotide repeat (TNR) tracts modulate repeat instability through the coordination among the key BER enzymes DNA polymerase β, flap endonuclease 1 (FEN1) and DNA ligase I (LIG I). However, it remains unknown whether BER cofactors can also alter TNR stability. In this study, we discovered that proliferating cell nuclear antigen (PCNA), a cofactor of BER, promoted CAG repeat deletion and removal of a CAG repeat hairpin during BER in a duplex CAG repeat tract and CAG hairpin loop, respectively. We showed that PCNA stimulated LIG I activity on a nick across a small template loop during BER in a duplex (CAG)₂₀ repeat tract promoting small repeat deletions. Surprisingly, we found that during BER in a hairpin loop, PCNA promote

SUBMITTER: Beaver JM 

PROVIDER: S-EPMC5333789 | biostudies-literature | 2016 Dec

REPOSITORIES: biostudies-literature