Replication timing and genetic instability

Abstract

Chromosomal moted (DSBs) They some mor types. are are that by common characteristic DNA are The translocations joined double-strand proto-oncogene in cancer inappropriately. of specific cells, are breaks MYC pro- and tu(on chromosome 8) often undergoes chromosomal translocation into the immunoglobulin heavy chain (IGH) locus on chromosome 14, which initiates B cell and plasma cell neoplasms in humans, including Burkitt lymphoma (1). This translocation places MYC under the control of the powerful IGH enhancer, resulting in strong MYC overexpression in lymphoid cells. It has been suggested that the spatial proximity of MYC and IGH in the nucleus, determined by chromatin folding, promotes this common translocation (2). On page 1277 of this issue, Peycheva et al. (3) report that replication timing mediates the IGH-MYC translocation. Furthermore, they infer that shared replication timing arises from the physical proximity of the two loci, resulting in a shared replication hub, where the MYC and IGH replication origins are synchronously activated.