DNA damage and eIF4G1 in breast cancer cells reprogram translation for survival and DNA repair mRNAs

ABSTRACT: The cellular response to DNA damage is mediated through multiple pathways that regulate and coordinate DNA repair, cell cycle arrest and cell death. We show that the DNA damage response (DDR) induced by ionizing radiation (IR) is coordinated in breast cancer cells by selective mRNA translation mediated by high levels of translation initiation factor eIF4G1. Increased expression of eIF4G1, common in breast cancers, was found to selectively increase translation of mRNAs involved in cell survival and the DDR, preventing autophagy and apoptosis (Survivin, HIF1α, XIAP), promoting cell cycle arrest (GADD45a, p53, ATRIP, Chk1) and DNA repair (53BP1, BRCA1/2, PARP, Rfc2-5, ATM, MRE-11, others). Reduced expression of eIF4G1, but not its homolog eIF4G2, greatly sensitizes cells to DNA damage b

ORGANISM(S): Homo sapiens

SUBMITTER: Jiri Zavadil 

PROVIDER: E-GEOD-41627 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress