Drosophila p53isoforms have overlapping and distinct functions in germline genome integrity and oocyte quality control

Abstract

Abstractp53 gene family members in humans and other organisms encode a large number of protein isoforms whose functions are largely undefined. Using Drosophila as a model, we find that a p53B isoform is expressed predominantly in the germline where it colocalizes with p53A into subnuclear bodies. It is only p53A, however, that mediates the apoptotic response to ionizing radiation in the germline and soma. In contrast, p53A and p53B both respond to meiotic DNA breaks and are required during oogenesis to prevent persistent germline DNA breaks, an activity that is more crucial when meiotic recombination is defective. We find that in oocytes with persistent DNA breaks p53A is required to activate a meiotic pachytene checkpoint. Our findings indicate that Drosophila p53 isoforms have DNA lesion and cell type-specific functions, with parallels to the functions of mammalian p53 family members in the genotoxic stress response and oocyte quality control.

The DNA Damage response and cell competition are p53- and Xrp1-dependent processes that suppress hyperplastic aneuploidy

“…Multiple p53-dependent DDR genes, the majority in our study, were Xrp1-dependent, including the pro-apoptotic gene hid . Even though hid- reporters have been used as readouts of p53 activity (Fan et al 2010; Zhang et al 2014; Ruiz-Losada et al 2021; Chakravarti et al 2022), they may be more accurately described as targets of Xrp1. Other Xrp1 targets include DNA repair genes, GstD1, and Jun-kinase signaling.…”