Cell cycle regulator of non-homologous end joining (CYREN)

Cell cycle regulator of non-homologous end joining (CYREN) is a microprotein encoded by the human CYREN gene (previously known as C7orf49, MRI, and other aliases), which plays a critical role as a **regulator of DNA repair pathway choice** following double-strand breaks (DSBs) in DNA. CYREN functions primarily as a **cell cycle-specific inhibitor of classical non-homologous end joining (NHEJ)** during the S and G2 phases, promoting error-free repair by homologous recombination (HR) when sister chromatids are available[1][3][4][5]. It acts via direct interaction with the Ku70/Ku80 heterodimer, protecting overhang break sites and suppressing NHEJ to maintain genome stability. In G1 phase, CYREN may enhance NHEJ activity. CYREN is not considered a direct core component of the NHEJ machinery, but instead modulates pathway choice, influencing cellular susceptibility to DNA damage and potential disease states such as cancer[1][2][3][4][5]. No drugs directly targeting CYREN are currently documented and there are no established biomarkers for its activity. Loss or dysregulation of CYREN is implicated in increased DNA repair errors, chromosomal aberrations, and potential risk for cancer due to defective DSB repair during the cell cycle[1][2][3].

Other names

CYRENMRIMRI-2C7orf49chromosome 7 open reading frame 49cell cycle regulator of NHEJModulator of retrovirus infection homologCYREN-1CYREN-2MGC5242FLJ27285FLJ22450

Inhibition of classical NHEJ by binding and modulating Ku70/80 activity in S/G2, thereby favoring error-free HR repair; Activation of NHEJ in G1 by facilitating damage response protein interactions with double-strand break chromatin