The canonical non-homologous end joining factor XLF promotes chromosomal deletion rearrangements in human cells.

ABSTRACT: Clastogen exposure can result in chromosomal rearrangements, including large deletions and inversions that are associated with cancer development. To examine such rearrangements in human cells, here we developed a reporter assay based on endogenous genes on chromosome 12. Using the RNA-guided nuclease Cas9, we induced two DNA double-strand breaks, one each in the GAPDH and CD4 genes, that caused a deletion rearrangement leading to CD4 expression from the GAPDH promoter. We observed that this GAPDH-CD4 deletion rearrangement activates CD4+ cells that can be readily detected by flow cytometry. Similarly, double-strand breaks in the LPCAT3 and CD4 genes induced an LPCAT3-CD4 inversion rearrangement resulting in CD4 expression. Stu

SUBMITTER: Bhargava R 

PROVIDER: S-EPMC6952595 | biostudies-literature | 2020 Jan

REPOSITORIES: biostudies-literature