GEOapplication/xmlftp://ftp.ncbi.nlm.nih.gov/geo/series/GSE320nnn/GSE320153/primaryOK200OtherHomo sapiensOtherhttps://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE320153GEOGSEfalseA chemical-genetic interaction map of the DNA damage responseThe DNA damage response (DDR) is a sophisticated network of cellular pathways whose perturbation leads to genome instability and is a key hallmark of oncogenesis. Here we present data from 32 genome-scale loss-of-function CRISPRi chemical-genetic screens with inhibitors targeting core constituents of the DDR machinery (PARP, ATR, ATM, DNAPK, and WEE1), as both single agents and in combination with PARP inhibitors. These experiments identify >1000 genes whose perturbation modifies the DDR and provides a rich resource to the DDR community. In addition, this compendium of functional genomics data reveals key principles governing the DDR and highlights a strong chemical-genetic interaction between loss of activity of the peroxiredoxin PRDX1 and all tested DDR inhibitors through a mechanism involving iron availability mediated by an MRGBP-PAX7-IREB2 axis. Our data position PRDX1 as a key suppressor of DNA damage accumulation and potential druggable target in combination with DDR inhibitors.2026/08/24GSE320153GSM9535762GSM9535784GSM9535785GSM9535763GSM9535764GSM9535786GSM9535765GSM9535787GSM9535780GSM9535781GSM9535782GSM9535760GSM9535761GSM9535783GSM9535788GSM9535766GSM9535767GSM9535768GSM9535769GSM9535773GSM9535751GSM9535752GSM9535774GSM9535753GSM9535775GSM9535776GSM9535754GSM9535770GSM9535771GSM9535772GSM9535759GSM9535755GSM9535777GSM9535756GSM9535778GSM9535779GSM9535757GSM95357582030124676320153Homo sapiens