Mechanistic basis for microhomology identification and genome scarring by polymerase theta.

ABSTRACT: DNA polymerase theta mediates an end joining pathway (TMEJ) that repairs chromosome breaks. It requires resection of broken ends to generate long, 3' single-stranded DNA tails, annealing of complementary sequence segments (microhomologies) in these tails, followed by microhomology-primed synthesis sufficient to resolve broken ends. The means by which microhomologies are identified is thus a critical step in this pathway, but is not understood. Here we show microhomologies are identified by a scanning mechanism initiated from the 3' terminus and favoring bidirectional progression into flanking DNA, typically to a maximum of 15 nucleotides into each flank. Polymerase theta is frequently insufficiently processive to complete repair of breaks in microhomology-poor, AT-rich regions. Aborted syn

SUBMITTER: Carvajal-Garcia J 

PROVIDER: S-EPMC7165422 | biostudies-literature | 2020 Apr

REPOSITORIES: biostudies-literature