The NEK1 interactor, C21ORF2, is required for efficient DNA damage repair.

Defective DNA damage response is a threat to genome stability and a proven cause of tumorigenesis. C21ORF2 (chromosome 21 open reading frame 2) is a novel gene on chromosome 21, and the C21ORF2 protein is found to interact with NEK1. Earlier studies showed that C21ORF2 might be associated with some human genetic diseases including Down syndrome. However, the cellular functions of C21ORF2 remain unknown. In the present study, we reported that C21ORF2 affected cell proliferation after DNA damage induced by ionizing radiation, and DNA repair was less efficient in C21ORF2-depleted cells compared with control cells. However, C21ORF2-knockdown cells did not show defects in the activation of the G2-phase DNA damage checkpoint. Furthermore, homologous recombination, but not non-homologous end joining repair, was found to be impaired after C21ORF2 attenuation, which could be rescued by the overexpression of NEK1, indicating that C21ORF2 functions in the same pathway as NEK1 in DNA damage repair.