Alternative end-joining is suppressed by the canonical NHEJ component Xrcc4-ligase IV during chromosomal translocation formation.

ABSTRACT: Chromosomal translocations in hematologic and mesenchymal tumors form overwhelmingly by nonhomologous end-joining (NHEJ). Canonical NHEJ, essential for the repair of radiation-induced and some programmed double-strand breaks (DSBs), requires the Xrcc4-ligase IV complex. For other DSBs, the requirement for Xrcc4-ligase IV is less stringent, suggesting the existence of alternative end-joining (alt-NHEJ) pathways. To understand the contributions of the canonical NHEJ and alt-NHEJ pathways, we examined translocation formation in cells deficient in Xrcc4-ligase IV. We found that Xrcc4-ligase IV is not required for but rather suppresses translocations. Translocation breakpoint junctions have similar characteristics in wild-type cells and cells deficient in Xrcc4-ligase IV, including an unchanged

SUBMITTER: Simsek D 

PROVIDER: S-EPMC3893185 | biostudies-literature | 2010 Apr

REPOSITORIES: biostudies-literature