TY  - JOUR
A1  - Körner, Maria
A1  - Meyer, Susanne R.
A1  - Marincola, Gabriella
A1  - Kern, Maximilian J.
A1  - Grimm, Clemens
A1  - Schuelein-Voelk, Christina
A1  - Fischer, Utz
A1  - Hofmann, Kay
A1  - Buchberger, Alexander
T1  - The FAM104 proteins VCF1/2 promote the nuclear localization of p97/VCP
JF  - eLife
N2  - The ATPase p97 (also known as VCP, Cdc48) has crucial functions in a variety of important cellular processes such as protein quality control, organellar homeostasis, and DNA damage repair, and its de-regulation is linked to neuromuscular diseases and cancer. p97 is tightly controlled by numerous regulatory cofactors, but the full range and function of the p97–cofactor network is unknown. Here, we identify the hitherto uncharacterized FAM104 proteins as a conserved family of p97 interactors. The two human family members VCP nuclear cofactor family member 1 and 2 (VCF1/2) bind p97 directly via a novel, alpha-helical motif and associate with p97-UFD1-NPL4 and p97-UBXN2B complexes in cells. VCF1/2 localize to the nucleus and promote the nuclear import of p97. Loss of VCF1/2 results in reduced nuclear p97 levels, slow growth, and hypersensitivity to chemical inhibition of p97 in the absence and presence of DNA damage, suggesting that FAM104 proteins are critical regulators of nuclear p97 functions.
KW  - p97 VCP Cdc48
KW  - ubiquitin proteasome system
KW  - nuclear import
KW  - DNA damage repair
KW  - FAM104A
KW  - FLJ14775
KW  - FAM104B
KW  - FLJ20434
KW  - CXorf44
KW  - cell biology
Y1  - 2023
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-350222
VL  - 12
ER  - 
TY  - JOUR
A1  - Schröder, Wiebke
A1  - Bernhardt, Jörg
A1  - Marincola, Gabriella
A1  - Klein-Hitpass, Ludger
A1  - Herbig, Alexander
A1  - Krupp, Guido
A1  - Nieselt, Kay
A1  - Wolz, Christiane
T1  - Altering gene expression by aminocoumarins: the role of DNA supercoiling in Staphylococcus aureus
JF  - BMC Genomics
N2  - BACKGROUND:
It has been shown previously that aminocoumarin antibiotics such as novobiocin lead to immediate downregulation of recA expression and thereby inhibit the SOS response, mutation frequency and recombination capacity in Staphylococcus aureus. Aminocoumarins function by inhibiting the ATPase activity of DNA gyrase subunit B with a severe impact on DNA supercoiling.
RESULTS:
Here, we have analysed the global impact of the DNA relaxing agent novobiocin on gene expression in S. aureus. Using a novobiocin-resistant mutant, it became evident that the change in recA expression is due to gyrase inhibition. Microarray analysis and northern blot hybridisation revealed that the expression levels of a distinct set of genes were increased (e.g., recF-gyrB-gyrA, the rib operon and the ure operon) or decreased (e.g., arlRS, recA, lukA, hlgC and fnbA) by novobiocin. The two-component ArlRS system was previously found to decrease the level of supercoiling in S. aureus. Thus, downregulation of arlRS might partially compensate for the relaxing effect of novobiocin. Global analysis and gene mapping of supercoiling-sensitive genes did not provide any indication that they are clustered in the genome. Promoter fusion assays confirmed that the responsiveness of a given gene is intrinsic to the promoter region but independent of the chromosomal location.
CONCLUSIONS:
The results indicate that the molecular properties of a given promoter, rather than the chromosomal topology, dictate the responsiveness to changes in supercoiling in the pathogen Staphylococcus aureus.
KW  - aminocoumarins
KW  - novobiocin
KW  - microarray
KW  - Voronoi tree map
KW  - spacer
KW  - arlR
KW  - gyrase
KW  - supercoiling
KW  - staphylococcus aureus
Y1  - 2014
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-121609
SN  - 1471-2164
VL  - 15
IS  - 291
ER  -