% IMPORTANT: The following is UTF-8 encoded. This means that in the presence
% of non-ASCII characters, it will not work with BibTeX 0.99 or older.
% Instead, you should use an up-to-date BibTeX implementation like “bibtex8” or
% “biber”.
@ARTICLE{Zhang:277705,
author = {L. Zhang$^*$ and M. Wirth$^*$ and U. Patra and J. Stroh$^*$
and K. Isaakidis$^*$ and L. Rieger and S. Kossatz$^*$ and M.
Milanovic$^*$ and C. Zang$^*$ and U. Demel$^*$ and J.
Keiten-Schmitz$^*$ and K. Wagner$^*$ and K. Steiger$^*$ and
R. Rad$^*$ and F. Bassermann$^*$ and S. Müller$^*$ and U.
Keller$^*$ and M. Schick$^*$},
title = {{A}ctionable loss of {SLF}2 drives {B}-cell lymphomagenesis
and impairs the {DNA} damage response.},
journal = {EMBO molecular medicine},
volume = {15},
number = {9},
issn = {1757-4676},
address = {Heidelberg},
publisher = {EMBO Press},
reportid = {DKFZ-2023-01422},
pages = {e16431},
year = {2023},
note = {2023 Sep 11;15(9):e16431},
abstract = {The DNA damage response (DDR) acts as a barrier to
malignant transformation and is often impaired during
tumorigenesis. Exploiting the impaired DDR can be a
promising therapeutic strategy; however, the mechanisms of
inactivation and corresponding biomarkers are incompletely
understood. Starting from an unbiased screening approach, we
identified the SMC5-SMC6 Complex Localization Factor 2
(SLF2) as a regulator of the DDR and biomarker for a B-cell
lymphoma (BCL) patient subgroup with an adverse prognosis.
SLF2-deficiency leads to loss of DDR factors including
Claspin (CLSPN) and consequently impairs CHK1 activation. In
line with this mechanism, genetic deletion of Slf2 drives
lymphomagenesis in vivo. Tumor cells lacking SLF2 are
characterized by a high level of DNA damage, which leads to
alterations of the post-translational SUMOylation pathway as
a safeguard. The resulting co-dependency confers synthetic
lethality to a clinically applicable SUMOylation inhibitor
(SUMOi), and inhibitors of the DDR pathway act highly
synergistic with SUMOi. Together, our results identify SLF2
as a DDR regulator and reveal co-targeting of the DDR and
SUMOylation as a promising strategy for treating aggressive
lymphoma.},
keywords = {CHK1 (Other) / DNA damage response (Other) / SLF2 (Other) /
SUMO (Other) / lymphoma (Other)},
cin = {BE01 / FM01 / MU01},
ddc = {610},
cid = {I:(DE-He78)BE01-20160331 / I:(DE-He78)FM01-20160331 /
I:(DE-He78)MU01-20160331},
pnm = {899 - ohne Topic (POF4-899)},
pid = {G:(DE-HGF)POF4-899},
typ = {PUB:(DE-HGF)16},
pubmed = {pmid:37485814},
doi = {10.15252/emmm.202216431},
url = {https://inrepo02.dkfz.de/record/277705},
}