The research focus of Subarea 4 is on studying damages of macromolecules (proteins, nucleic acids) and determining the structure-function relationship of biomolecules relevant to damage and damage repair processes and responses to molecular damage that might lead to aging and aging-associated pathologies.
The studies are focused on the following research areas: DNA replication, DNA damage responses (DDR), stress responses, metabolic stresses, protein trafficking and protein damages.
The research is defined by four focus areas:
- DNA damage response in tissue homeostasis and neuropathies,
- Quality control in the endoplasmic reticulum for secretory pathway in aging processes,
- Intrinsic and extrinsic factors implicated in cellular decline during aging, and
- DNA replication and genomic integrity preventing premature aging and diseases.
Research focus of Subarea 4.
The accumulation of damaged macromolecules or subcellular organelles is associated with dysfunction of a cell, which contributes to tissue & organ failure. DNA damage, genomic instability, protein misfolding or defects in toxic protein degradation can compromise cell functionality. Alterations of mitochondrial DNA and protein complexes affect cellular metabolism, which will have a general impact on cell integrity.
- Disease-causing mutated ATLASTIN 3 is excluded from distal axons and reduces axonal autophagy.
Behrendt L, Hoischen C, Kaether C
Neurobiol Dis 2021, 155, 105400
- Nbs1-mediated DNA damage repair pathway regulates haematopoietic stem cell development and embryonic haematopoiesis.
Chen Y, Sun J, Ju Z, Wang ZQ, Li T
Cell Prolif 2021, 54(3), e12972
- Conserved exchange of paralog proteins during neuronal differentiation
Di Fraia D, Anitei M, Mackmull MT, Parca L, Behrendt L, Andres-Pons A, Gilmour D, Helmer Citterich M, Kaether C, Beck M, Ori A
bioRxiv 2021, doi.org/10.1101/2021.07.22.45334
- GMPPA defects cause a neuromuscular disorder with α-dystroglycan hyperglycosylation.
Franzka P, Henze* H, Jung* MJ, Schüler SC, Mittag S, Biskup K, Liebmann L, Kentache T, Morales J, Martínez B, Katona I, Herrmann T, Huebner AK, Hennings JC, Groth S, Gresing LJ, Horstkorte R, Marquardt T, Weis J, Kaether C, Mutchinick OM, Ori A, Huber O, Blanchard V, von Maltzahn J, Hübner CA
J Clin Invest 2021, 131(9), e139076 * equal contribution
- Establishment of a fluorescent reporter of RNA-polymerase II activity to identify dormant cells
Freter R, Falletta P, Omrani O, Rasa M, Herbert K, Annunziata F, Minetti A, Krepelova A, Adam L, Käppel S, Rüdiger T, Wang ZQ, Goding** CR, Neri** F
Nat Commun 2021, 12(1), 3318 ** co-corresponding authors
- ATR regulates neuronal activity by modulating presynaptic firing.
Kirtay M, Sell J, Marx C, Haselmann H, Ceanga M, Zhou ZW, Rahmati V, Kirkpatrick J, Buder K, Grigaravicius P, Ori A, Geis** C, Wang** ZQ
Nat Commun 2021, 12(1), 4067 ** co-corresponding authors
- The Role of the Pathogen Dose and PI3Kγ in Immunometabolic Reprogramming of Microglia for Innate Immune Memory.
Lajqi T, Marx C, Hudalla H, Haas F, Große S, Wang ZQ, Heller R, Bauer M, Wetzker R, Bauer R
Int J Mol Sci 2021, 22(5)
- MAPK10 Expression as a Prognostic Marker of the Immunosuppressive Tumor Microenvironment in Human Hepatocellular Carcinoma.
Li H, Li Y, Zhang Y, Tan B, Huang T, Xiong J, Tan X, Ermolaeva** MA, Fu** L
Front Oncol 2021, 11, 687371 ** co-corresponding authors
- The N-terminal BRCT domain determines MCPH1 function in brain development and fertility.
Liu* X, Schneble-Löhnert* N, Kristofova M, Qing X, Labisch J, Hofmann S, Ehrenberg S, Sannai M, Jörß T, Ori A, Godmann M, Wang ZQ
Cell Death Dis 2021, 12(2), 143 * equal contribution
- Post-Translational Modification of MRE11: Its Implication in DDR and Diseases.
Lu R, Zhang H, Jiang YN, Wang ZQ, Sun L, Zhou ZW
Genes (Basel) 2021, 12(8)