GINS complex subunit 4 (GINS4)

GINS complex subunit 4 (GINS4, also known as SLD5) is one of four proteins forming the GINS complex, a tetramer crucial for DNA replication in eukaryotic cells. The GINS complex functions as part of the CMG helicase, which unwinds DNA during replication and orchestrates the formation and progression of replication forks. GINS4 is required for proper cell cycle progression, ensuring stability of the genome and supporting cellular proliferation. Aberrant regulation or overexpression of GINS4 is linked to various cancers including lung adenocarcinoma, where it acts as an oncogene by suppressing ferroptosis through p53 acetylation pathways. Knockout or inhibition of GINS4 has been shown to promote cell death via ferroptosis, particularly in cancer cells. While GINS4 is an emerging cancer therapeutic target, no approved drugs currently act on it directly. Its essential role in DNA replication also raises safety concerns regarding toxicity in normal proliferating tissues[1][2][3][4].

Other names

DNA replication complex GINS protein SLD5GINS4SLD5MGC14799SLD5 homolog

Hypothetical: Inhibition of GINS4 could arrest DNA replication in cancer cells, induce ferroptosis by enhancing p53 function, or prevent cell cycle progression at replication forks[2][4]. Therapeutic mechanism (preclinical): Chemotherapy drugs that trap tumor cells in G2/M phase may synergize with GINS4 inhibition to induce ferroptosis[2]. No approved drugs with defined mechanism for GINS4.