Research Area A
Publications 2014

We report the development of a new heterobase that is held together through reversible bonding. The so-formed cross-link adds strong stabilization to the DNA duplex. Despite this, the cross-link opens and closes through reversible imine bonding. Moreover, even enzymatic incorporation of the cross-link is possible. The new principle can be used to stabilize DNA ... READ MORE

Cells cope with replication-blocking lesions via translesion DNA synthesis (TLS). TLS is carried out by low-fidelity DNA polymerases that replicate across lesions, thereby preventing genome instability at the cost of increased point mutations. Here we perform a two-stage siRNA-based functional screen for mammalian TLS genes and identify 17 validated TLS genes. One ... READ MORE

UV excitation of the DNA single strand (dT)₁₈ leads to electronically excited states that are potential gateways to DNA photolesions. Using time-resolved infrared spectroscopy we characterized a species with a lifetime of ̴100 ps and identified it as a charge separated excited state between two thymine bases. ... READ MORE

Resistance to chemotherapeutic agents represents a major challenge in cancer research. One approach to this problem is combination therapy, the application of a toxic chemotherapeutic drug together with a sensitizing compound that addresses the vulnerability of cancer cells to induce apoptosis. Here we report the discovery of a new compound class (T8) that sensitizes ... READ MORE

Hemithioindigo (HTI) photoswitches have a tremendous potential for biological and supramolecular applications due to their absorptions in the visible-light region in conjunction with ultrafast photoisomerization and high thermal bistability. Rational tailoring of the photophysical properties for a specific application is the key to exploit the full potential of HTIs ... READ MORE

Excited-state dynamics are essential to understanding the formation of DNA lesions induced by UV light. By using femtosecond IR spectroscopy, it was possible to determine the lifetimes of the excited states of all four bases in the double-stranded environment of natural DNA. After UV excitation of the DNA duplex, we detected a concerted decay of base pairs connected ... READ MORE

The DNA structure is an ideal building block for the construction of functional nano-objects. In this direction, metal coordinating base pairs (ligandosides) are an appealing tool for the future specific functionalization of such nano-objects. We present here a study, in which we combine the metal ion coordinating pyrazole ligandoside with the interstrand ... READ MORE

Living organisms protect the genome against external influences by recognizing and repairing damaged DNA. A common source of gene mutation is the oxidized guanine, which undergoes base excision repair through cleavage of the glycosidic bond between the ribose and the nucleobase of the lesion. We unravel the repair mechanism utilized by bacterial glycosylase, MutM, ... READ MORE

Ten eleven translocation (Tet) enzymes oxidize the epigenetically important DNA base 5-methylcytosine (mC) stepwise to 5-hydroxymethylcytosine (hmC), 5-formylcytosine and 5-carboxycytosine. It is currently unknown whether Tet-induced oxidation is limited to cytosine-derived nucleobases or whether other nucleobases are oxidized as well. We synthesized isotopologs of ... READ MORE

The primary dynamics of reaction centers from Rhodobacter sphaeroides at room temperature are studied at low excitation intensities and low excitation rates. Analysis based on singular value decomposition yields three time constants in the picosecond range (ca. 1.2 ps, 3.5 ps and 220 ps). The spectral and temporal signatures are fully consistent with the step-wise ... READ MORE

The decay of triplet states and the formation of cyclobutane pyrimidine dimers (CPDs) after UV excitation of the all-thymine oligomer (dT)18 and the locked dinucleotide TLpTL were studied by nanosecond IR spectroscopy. IR marker bands characteristic for the CPD lesion and the triplet state were observed from 1 ns (time resolution of the setup) onward. The amplitudes ... READ MORE

Base stacking in DNA is related to long-living excited states whose molecular nature is still under debate. To elucidate the molecular background we study well-defined oligonucleotides with natural bases, which allow selective UV excitation of one single base in the strand. IR probing in the picosecond regime enables us to dissect the contribution of different single ... READ MORE

Pyridoxal 5′-phosphate (PLP) is the active vitamer of vitamin B6 and acts as an essential cofactor in many aspects of amino acid and sugar metabolism. The virulence and survival of pathogenic bacteria such as Mycobacterium tuberculosis depend on PLP, and deficiencies in humans have also been associated with neurological disorders and inflammation. While PLP can be ... READ MORE

Methylated cytidine plays an important role as an epigenetic signal in gene regulation. Its oxidation products are assumed to be involved in active demethylation processes but also in damaging DNA. Here, we report the photochemical production of the 5-methyl-2′-deoxycytidine radical cation via a two-photon ionization process. The radical cation is detected by ... READ MORE

Conformational changes in proteins and peptides can be initiated by diverse processes. This raises the question how the variation of initiation mechanisms is connected to differences in folding or unfolding processes. In this work structural dynamics of a photoswitchable β-hairpin model peptide were initiated by two different mechanisms: temperature jump (T-jump) ... READ MORE

Die photochemischen Eigenschaften des Indigo, eines weit verbreiteten industriellen Produkts, haben von Anfang an das Interesse von Wissenschaftlern geweckt. Die Photostabilität von Indigo war Gegenstand intensiver Forschungen. In neuerer Zeit wurde vorgeschlagen, dass nach Photoanregung ein intramolekularer Protonentransfer auftritt, der gefolgt von einem ... READ MORE

Excimer formation and dissociation in 9,10-dichloroanthracene is investigated in solution phase (low/high concentration) and monocrystalline state (α/β structure) at room temperature by ultrafast absorption spectroscopy combined with streak-camera fluorescence experiments. The transition from the monomeric to the excimeric state is accompanied by a red-shift of the ... READ MORE

Despite their structural similarity, the natural products omuralide and vibralactone have different biological targets. While omuralide blocks the chymotryptic activity of the proteasome with an IC50 value of 47 nM, vibralactone does not have any effect at this protease up to a concentration of 1 mM. Activity-based protein ... READ MORE

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