Genome instability triggered by the V(D)J recombination by-product

Christopher M Kirkham; Joan Boyes

doi:10.1080/23723556.2019.1610323

Genome instability triggered by the V(D)J recombination by-product

Mol Cell Oncol. 2019 May 7;6(4):1610323. doi: 10.1080/23723556.2019.1610323. eCollection 2019.

Authors

Christopher M Kirkham¹, Joan Boyes²

Affiliations

¹ Discovery Services, Charles River Laboratories, Inc, Bristol, UK.
² School of Molecular and Cellular Biology, Faculty of Biological Sciences, University of Leeds, Leeds, UK.

Abstract

A newly identified process by which mistargeted V(D)J recombination could cause genome instability in childhood leukemia has been discovered. In this mechanism, called cut-and-run, the excised DNA by-products of V(D)J recombination are re-bound by the recombinase proteins and erroneously trigger double-strand breaks at multiple locations throughout the genome. Many of these breakpoints co-localize with known chromosome alterations in acute lymphoblastic leukemia (ALL).

Keywords: RAG recombinase; V(D)J recombination; acute lymphoblastic leukemia; chromosome translocations; double strand breaks; genome instability.

Grants and funding

This work was supported by a Bloodwise research grant (15042) and an Engineering and Physical Sciences Research Council studentship (EP/P505593/1 to C.M.K.).