Cut-and-Run: A Distinct Mechanism by which V(D)J Recombination Causes Genome Instability.

ABSTRACT: V(D)J recombination is essential to generate antigen receptor diversity but is also a potent cause of genome instability. Many chromosome alterations that result from aberrant V(D)J recombination involve breaks at single recombination signal sequences (RSSs). A long-standing question, however, is how such breaks occur. Here, we show that the genomic DNA that is excised during recombination, the excised signal circle (ESC), forms a complex with the recombinase proteins to efficiently catalyze breaks at single RSSs both in vitro and in vivo. Following cutting, the RSS is released while the ESC-recombinase complex remains intact to potentially trigger breaks at further RSSs. Consistent with this, chromosome breaks at RSSs increase markedly in the presence of the ESC. Notably, these breaks co-

SUBMITTER: Kirkham CM 

PROVIDER: S-EPMC6509286 | biostudies-literature | 2019 May

REPOSITORIES: biostudies-literature