This has to do with the different hyphenation algorithm used by LuaTeX. I don't really know the details, but here's what's shown when I put DNA-Sequenzierung and \acs{DNA}-Sequenzierung in a box and make LuaTeX show it.
\sbox0{DNA-Sequenzierung}
\hbox(6.8872+1.94397)x88.4784, direction TLT
.\T1/cmr/m/n/10 D
.\T1/cmr/m/n/10 N
.\T1/cmr/m/n/10 A
.\T1/cmr/m/n/10 -
.\discretionary
.\T1/cmr/m/n/10 S
.\T1/cmr/m/n/10 e
.\T1/cmr/m/n/10 q
.\T1/cmr/m/n/10 u
.\T1/cmr/m/n/10 e
.\T1/cmr/m/n/10 n
.\T1/cmr/m/n/10 z
.\T1/cmr/m/n/10 i
.\T1/cmr/m/n/10 e
.\T1/cmr/m/n/10 r
.\T1/cmr/m/n/10 u
.\T1/cmr/m/n/10 n
.\T1/cmr/m/n/10 g
\sbox0{\acs{DNA}-Sequenzierung}
\hbox(6.8872+1.94397)x88.4784, direction TLT
.\hbox(6.8872+0.0)x22.63336, direction TLT
..\hbox(6.8872+0.0)x22.63336, direction TLT
..\hbox(6.8872+0.0)x0.0, glue set - 22.63336fil, direction TLT
...\glue 0.0 plus 1.0fil minus 1.0fil
...\T1/cmr/m/n/10 D
...\T1/cmr/m/n/10 N
...\T1/cmr/m/n/10 A
.\T1/cmr/m/n/10 -
.\T1/cmr/m/n/10 S
.\T1/cmr/m/n/10 e
.\T1/cmr/m/n/10 q
.\T1/cmr/m/n/10 u
.\T1/cmr/m/n/10 e
.\T1/cmr/m/n/10 n
.\T1/cmr/m/n/10 z
.\T1/cmr/m/n/10 i
.\T1/cmr/m/n/10 e
.\T1/cmr/m/n/10 r
.\T1/cmr/m/n/10 u
.\T1/cmr/m/n/10 n
.\T1/cmr/m/n/10 g
In the first case LuaTeX puts a \discretionary item after the hyphen, while it doesn't in the second case, probably because it thinks that the hyphen is at the start of a word (it comes after a box which is not part of the word).
This does not happen with pdfLaTeX, because the \discretionary item is inserted at a later stage.
It's probably better, in any case, using the babel shortcuts:
Das ist ein sehr langer Satz und er wird an seinem Ende leider
nicht richtig umgebrochen: DNA"=Sequenzierung
Das ist ein sehr langer Satz und er wird an seinem Ende leider
nicht richtig umgebrochen: \acs{DNA}"=Sequenzierung
which gives

DNA-by writing\acs{DNA}-\hspace{0pt}Sequenzierung. If this sequence (pun intended) occurs frequently in your document, you may want to consider creating a little macro, such as\newcommand{\DNAS}{\acs{DNA}-\hspace{0pt}Sequenzierung}. – Mico Mar 21 at 5:26