If the question is "have you any experience using Microsoft Word?" and you do not, the answer is simply "no". If the question is more general and pertaining to the job you are applying for than the answer will never be just "no". Why are you applying for that job? At that company? Your reply will be something like "no, I've never done <that> but I've always wanted to ..... " and this is where you get creative, sell yourself, and show you've done your homework. "No, I've never used a cash register before but I want to become a manager and maybe own my own Subway one day and to do so I will need to learn how to do all jobs .... " Basically you need to communicate that even if you are lacking some skills you want this job with this company and are willing to learn. I hope this helps.