Fig. 8: preL-MMEJ deletions are the result of alternative DSB repair pathway mediated by PARP1 and replication associated DNA polymerases.
From: Recurrent deletions in clonal hematopoiesis are driven by microhomology-mediated end joining
Three distinct pathways of double strand breaks (DSBs) and their consequent repair outcomes. Classical non-homologous end-joining (c-NHEJ) which involves a final ligation step by LIG4, results in short deletions (<5-bp) or insertions at the breakpoint. Homologous recombination (HR) is an error free repair. Both c-NHEJ and alternative end-joining (alt-EJ) pathways are regulated by PARP1. PARP1 is involved in the formation of c-NHEJ related insertions together with the activation of POLQ and other replication associated DNA polymerases. POLQ mediated pathway generates ≥5-bp deletions that are flanked by microhomologies (MHs) of at least 2 bp. However, preL-MMEJ deletions are only mildly contributed by POLQ (thin arrow) while mainly contributed by other replication associated DNA polymerases (thick arrow).
