Paralog of XRCC4 and XLF (PAXX) (PAXX)

Paralog of XRCC4 and XLF (PAXX) is a recently characterized protein that acts as an accessory component of the non-homologous end joining (NHEJ) pathway for DNA double-strand break (DSB) repair. PAXX structurally resembles XRCC4 and XLF and interacts directly with the Ku70/Ku80 heterodimer, facilitating assembly and stabilization of the NHEJ complex at DSB sites. PAXX supports DNA end synapsis and promotes recruitment of DNA ligase IV and other core NHEJ factors. Loss of PAXX, particularly when combined with loss of XLF or inhibition of DNA-PKcs, impairs NHEJ efficiency, emphasizing its role in safeguarding genomic integrity. Overexpression of PAXX has been linked to poor prognosis and drug resistance in certain cancers, highlighting its potential relevance as a biomarker and therapeutic target in oncology. No small-molecule drugs are known to directly target PAXX, but its expression and function influence cellular response to DNA damage and chemotherapeutic agents.

Other names

C9orf142XLSXRCC4-like small proteinprotein PAXXparalog of XRCC4 and XLF

Not directly targeted by drugs, but implicated in cellular resistance to chemotherapeutic agents such as oxaliplatin and 5-fluorouracil through NHEJ pathway activity modulation.