UC San Diego

The Schlafen family of proteins have relatively unknown molecular mechanisms and biological functions. Here we study the novel functions of one member in the human Slfn family, huSlfn11, and its role in regulating the DNA damage response (DDR) as well as its ability to stabilize Z-DNA. We found that huSlfn11-expressing cancer cells treated with camptothecin (CPT) display selective inhibition of ATR (ataxia-telangiectasia mutated and RAD3- related) protein translation efficiency. This selective regulation by huSlfn11 is based on the codon usage of ATR. We have also demonstrated that cancer cells deficient in huSlfn11 expression can be completely re-sensitized to CPT by knocking down the expression of ATR, and moderately re- sensitizied to CPT with the use of ATR inhibitors. Additionally, we have shown for the first time, that huSlfn11N, the C-terminal truncation of full length huSlfn11 that includes the ATPase AAA domain, can stabilize Z-DNA conformation, possibly as a novel antiviral mechanism