TRF2-mediated telomere protection is dispensable in pluripotent stem cells.

ABSTRACT: In mammals, telomere protection is mediated by the essential protein TRF2, which binds chromosome ends and ensures genome integrity^1,2. TRF2 depletion results in end-to-end chromosome fusions in all cell types that have been tested so far. Here we find that TRF2 is dispensable for the proliferation and survival of mouse embryonic stem (ES) cells. Trf2^-/- (also known as Terf2) ES cells do not exhibit telomere fusions and can be expanded indefinitely. In response to the deletion of TRF2, ES cells exhibit a muted DNA damage response that is characterized by the recruitment of γH2AX-but not 53BP1-to telomeres. To define the mechanisms that control this unique DNA damage response in ES cells, we performed a CRISPR-Cas9-knockout screen. We found a strong dependency of TRF2-

SUBMITTER: Markiewicz-Potoczny M 

PROVIDER: S-EPMC9161009 | biostudies-literature | 2021 Jan

REPOSITORIES: biostudies-literature