ZNF512B protects critical regulatory regions to safeguard long term genomic integrity. [screening]

ZNF512B depletion induces SASP, and its overexpression inhibits SASP in various in vitro and in vivo models by modulating DNA repair. ZNF512B overexpression slows down cutaneous wound healing and reduces damage associated with acute liver injury by repression of SASP. ZNF512B is a known prognostic factor for amyotrophic lateral sclerosis (ALS) (Jiang et al., 2021; Tetsuka et al., 2013; Yang et al., 2015; Yu et al., 2018) and its ablation in human neuromuscular organoids leads to depletion of astroglia compartment, a possible mechanism leading to subsequent defects in neuromuscular pathology in ALS.

Taken together these findings have important implications for our understanding of repair bias around functionally constrained regions to safeguard long term genome integrity during aging and age associated pathology.