Replication stress at microsatellites causes DNA double-strand breaks and break-induced replication.

ABSTRACT: Short tandemly repeated DNA sequences, termed microsatellites, are abundant in the human genome. These microsatellites exhibit length instability and susceptibility to DNA double-strand breaks (DSBs) due to their tendency to form stable non-B DNA structures. Replication-dependent microsatellite DSBs are linked to genome instability signatures in human developmental diseases and cancers. To probe the causes and consequences of microsatellite DSBs, we designed a dual-fluorescence reporter system to detect DSBs at expanded (CTG/CAG) _n and polypurine/polypyrimidine (Pu/Py) mirror repeat structures alongside the c-myc replication origin integrated at a single ectopic chromosomal site. Restriction cleavage near the (CTG/CAG)₁₀₀ microsatellite leads to homology

SUBMITTER: Gadgil RY 

PROVIDER: S-EPMC7650239 | biostudies-literature | 2020 Nov

REPOSITORIES: biostudies-literature