POGZ promotes homology-directed DNA repair in an HP1-dependent manner

ABSTRACT: The heterochromatin protein HP1 plays a central role in the maintenance of genome stability but little is known about how HP1 is controlled. Here, we show that the zinc finger protein POGZ promotes the presence of HP1 at DNA double-strand breaks (DSBs) in human cells. POGZ depletion delays the resolution of DSBs and sensitizes cells to different DNA damaging agents, including cisplatin and talazoparib. Mechanistically, POGZ promotes homology-directed DNA repair by retaining the BRCA1/BARD1 complex at DSBs in an HP1-dependent manner. In vivo CRISPR inactivation of Pogz is embryonically lethal. Pogz haplo-insufficiency (Pogz+/delta) results in developmental delay, impaired intellectual abilities, hyperactive behavior and a compromised humoral immune response in mice, recapitulating the main

SUBMITTER: Mr. John Heath 

PROVIDER: S-SCDT-EMBOR-2020-51041V1 | biostudies-other |

REPOSITORIES: biostudies-other