The cancer testes antigen, HORMAD1, limits genomic instability in cancer cells by protecting stalled replication forks.

ABSTRACT: Tumors anomalously induce the expression of meiotic genes, which are otherwise restricted only to developing gametes. If and how these aberrantly expressed meiotic proteins influence DNA metabolism is not clear, but could have important implications for how tumors acquire and mitigate genomic instability. HORMAD1 is a highly conserved meiotic protein that is frequently expressed in lung adenocarincoma where its expression correlates with reduced patient survival and increased mutation burden. Here, we find that HORMAD1 associates with the replisome and is critical for protecting stalled DNA replication forks. Loss of HORMAD1 leads to nascent DNA strand degradation, an event which is mediated by the MRE11-DNA2-BLM pathway. We find that these phenotypes are due to limited RAD51 loading onto

SUBMITTER: Herrera LR 

PROVIDER: S-EPMC10656231 | biostudies-literature | 2023 Nov

REPOSITORIES: biostudies-literature