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the Demon Hunter has the skill which can mark an enemy for a 12% damage increase.

Do you have to assign them to the left or right mouse button to mark an enemy, or can I use the keyboard shortcuts 1-2-3-4 to mark?

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Did you try Elective mode (Options -> Gameplay -> Interface) –  Alok May 28 '12 at 5:41
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up vote 10 down vote accepted

Start a game, go to Options -> Gameplay and turn on elective mode.

You can then right click any skill slot (or choose the slot on the skill screen) and assign a skill from any category to it. There will be arrows on either side of the bar where the skills are shown for you to scroll between categories.

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Just tried using it; as I mentioned earlier you can turn on Elective Mode to assign it to the mouse buttons.

Also, it is in the defensive category #2, and works just fine using the '2' keyboard shortcut by default.

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