RAD54-like protein 2 (RAD54L2)

RAD54-like protein 2 (RAD54L2), also known as ARIP4, is an SNF2-family ATP-dependent DNA helicase and chromatin remodeler. It is fundamental in maintaining genome stability through its unique DNA damage avoidance pathway that regulates topoisomerase II (TOP2) turnover and suppresses formation of deleterious DNA adducts and recombination intermediates. RAD54L2 collaborates with factors like BLM/TOP3A/RMI1/RMI2 complexes, modulating post-replication repair, DNA damage response, and transcriptional regulation. It physically interacts with androgen receptor and is enriched at promoter regions needing rapid transcriptional induction, such as androgen-regulated genes. RAD54L2 deficiency sensitizes cells to chemotherapeutics targeting TOP2 due to enhanced persistence of TOP2-DNA adducts and chromosomal aberrations. Loss of RAD54L2 causes increased sister chromatid exchanges, decreased recombination repair fidelity, and heightened genome instability. Thus, RAD54L2 is a central guardian of chromatin integrity, cellular response to DNA damage, and is implicated in cancer biology, especially in relation to chemotherapy sensitivity.

Other names

Helicase ARIP4ARIP4KIAA0809SRISNF2LAndrogen receptor-interacting protein 4RAD54-like protein 2AR interacting protein 4HSPC325

Drugs such as etoposide and doxorubicin trap TOP2-DNA cleavage complex intermediates (TOP2ccs); RAD54L2 mediates removal/resolution of these adducts, reducing drug-induced genotoxicity and cell sensitivity. Loss of RAD54L2 sensitizes cells to these agents, indicating its role in DNA damage avoidance