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Human polymerase theta helicase positions DNA microhomologies for double-strand break repair.


ABSTRACT: DNA double-strand breaks occur in all human cells on a daily basis and must be repaired with high fidelity to minimize genomic instability1. Deficiencies in high-fidelity DNA repair by homologous recombination lead to dependence on DNA polymerase theta, which identifies DNA microhomologies in 3' single-stranded DNA overhangs and anneals them to initiate error-prone double-strand break repair. The resulting genomic instability is associated with numerous cancers, thereby making this polymerase an attractive therapeutic target2,3. However, despite the biomedical importance of polymerase theta, the molecular details of how it initiates DNA break repair remain unclear4,5. Here we present cryo-electron microscopy structures of the polymerase theta helicase domai

SUBMITTER: Zerio CJ 

PROVIDER: S-EPMC11071473 | biostudies-literature | 2024 Apr

REPOSITORIES: biostudies-literature