Impact of bistrand abasic sites and proximate orientation on DNA global structure and duplex energetics

Minetti, Conceição A.S.A.; Sun, Jeffrey; Jacobs, Daniel P.; Kang, In-Koo; Remeta, David P.; Breslauer, Kenneth J.

doi:10.1002/bip.23098

Cited by 16 publications

(15 citation statements)

References 59 publications

(155 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…We previously demonstrated that the acetylation of OGG1 enhances its catalytic turnover by reducing its affinity for AP sites in DNA (24). The generation of an AP site significantly impacts the thermal stability of duplex DNA, unlike 8-oxoG paired with C (56); therefore, we propose that the generation of an AP site in a PQS after excision of an 8-oxoG by OGG1 destabilizes and opens up the duplex (57,58). Subsequent binding and stable coordination of APE1 with AP site in PQS promotes the formation and stabilization of a G-quadruplex structure with the AP site containing G track looped out.…”

Section: Discussionmentioning

confidence: 91%

Endogenous oxidized DNA bases and APE1 regulate the formation of G-quadruplex structures in the genome

Roychoudhury

Pramanik

Harris

et al. 2020

Proc. Natl. Acad. Sci. U.S.A.

View full text Add to dashboard Cite

Formation of G-quadruplex (G4) DNA structures in key regulatory regions in the genome has emerged as a secondary structure-based epigenetic mechanism for regulating multiple biological processes including transcription, replication, and telomere maintenance. G4 formation (folding), stabilization, and unfolding must be regulated to coordinate G4-mediated biological functions; however, how cells regulate the spatiotemporal formation of G4 structures in the genome is largely unknown. Here, we demonstrate that endogenous oxidized guanine bases in G4 sequences and the subsequent activation of the base excision repair (BER) pathway drive the spatiotemporal formation of G4 structures in the genome. Genome-wide mapping of occurrence of Apurinic/apyrimidinic (AP) site damage, binding of BER proteins, and G4 structures revealed that oxidized base-derived AP site damage and binding of OGG1 and APE1 are predominant in G4 sequences. Loss of APE1 abrogated G4 structure formation in cells, which suggests an essential role of APE1 in regulating the formation of G4 structures in the genome. Binding of APE1 to G4 sequences promotes G4 folding, and acetylation of APE1, which enhances its residence time, stabilizes G4 structures in cells. APE1 subsequently facilitates transcription factor loading to the promoter, providing mechanistic insight into the role of APE1 in G4-mediated gene expression. Our study unravels a role of endogenous oxidized DNA bases and APE1 in controlling the formation of higher-order DNA secondary structures to regulate transcription beyond its well-established role in safeguarding the genomic integrity.

show abstract

Section: Discussionmentioning

confidence: 91%

Endogenous oxidized DNA bases and APE1 regulate the formation of G-quadruplex structures in the genome

Roychoudhury

Pramanik

Harris

et al. 2020

Proc. Natl. Acad. Sci. U.S.A.

View full text Add to dashboard Cite

show abstract

“…It should be noted that although the right-handed, A-form helical structure is not significantly altered, there is a decrease in the magnitude of CD between the standard buffer and 20% PEG 200 curves at certain wavelength ranges (∼250–280 nm). The magnitude of CD depends largely on the spatial orientation of each base chromophore (38). It is, therefore, plausible that the addition of 20% PEG 200 results in a slight alteration of the spatial orientation of each base chromophore without affecting the global structure of the helix.…”

Section: Resultsmentioning

confidence: 99%

“…It is, therefore, plausible that the addition of 20% PEG 200 results in a slight alteration of the spatial orientation of each base chromophore without affecting the global structure of the helix. This shift has the potential to affect the energetics of the helix and have an overall destabilizing effect on the stability of the duplexes (38).…”

Section: Resultsmentioning

confidence: 99%

Thermodynamic characterization and nearest neighbor parameters for RNA duplexes under molecular crowding conditions

Adams

Znosko

2019

Nucleic Acids Research

View full text Add to dashboard Cite

It is essential to study RNA under molecular crowding conditions to better predict secondary structures of RNAs in vivo . No systematic study has been completed to determine the effects of molecular crowding on RNA duplexes of varying lengths and sequence composition. Here, optical melting, circular dichroism, and osmometry data were collected for RNA duplexes in a 20% polyethylene glycol (with an average molecular weight of 200 g/mol) solution (PEG 200), and nearest neighbor parameters were derived using this data. RNA duplexes are destabilized, on average, 1.02 kcal/mol in the presence of 20% PEG 200. The ΔG° 37 values predicted by the nearest neighbor parameters for RNA duplexes in 20% PEG 200 were ∼0.65 kcal/mol closer to experimental Δ G ° 37 values than those predicted by the standard nearest neighbor model. For one DNA sequence in solution with small crowders, the Δ G ° 37 values predicted by the 20% PEG 200 RNA nearest neighbor parameters were closer to the experimental values than Δ G ° 37 values predicted by either the RNA or DNA standard nearest neighbor models. This indicates that the nearest neighbor parameters for RNA duplexes in 20% PEG 200 may be generalizable to RNA and DNA duplexes in solutions with small crowding agents.

show abstract

“…Contrarily, the nine base pairs dsDNA region would preclude Bsu LigD from gain access to the AP site placed at the tenth position (Figure 5D). It has been described that the presence of an AP site can significantly alter the thermodynamic properties of a duplex destabilizing thermally and thermodynamically the DNA (40,41). Therefore, altogether the results led us to propose that the presence of an AP site proximal to a 5′-end could promote the partial melting of the recessive terminus.…”

Section: Resultsmentioning

confidence: 99%

Bacterial Ligase D preternary-precatalytic complex performs efficient abasic sites processing at double strand breaks during nonhomologous end joining

Ory

Carabaña

Vega

2019

Nucleic Acids Research

View full text Add to dashboard Cite

Abasic (AP) sites, the most common DNA lesions are frequently associated with double strand breaks (DSBs) and can pose a block to the final ligation. In many prokaryotes, nonhomologous end joining (NHEJ) repair of DSBs relies on a two-component machinery constituted by the ring-shaped DNA-binding Ku that recruits the multicatalytic protein Ligase D (LigD) to the ends. By using its polymerization and ligase activities, LigD fills the gaps that arise after realignment of the ends and seals the resulting nicks. Here, we show the presence of a robust AP lyase activity in the polymerization domain of Bacillus subtilis LigD ( Bsu LigD) that cleaves AP sites preferentially when they are proximal to recessive 5′-ends. Such a reaction depends on both, metal ions and the formation of a Watson–Crick base pair between the incoming nucleotide and the templating one opposite the AP site. Only after processing the AP site, and in the presence of the Ku protein, Bsu LigD catalyzes both, the in-trans addition of the nucleotide to the 3′-end of an incoming primer and the ligation of both ends. These results imply that formation of a preternary-precatalytic complex ensures the coupling of AP sites cleavage to the end-joining reaction by the bacterial LigD.

show abstract

Impact of bistrand abasic sites and proximate orientation on DNA global structure and duplex energetics

Cited by 16 publications

References 59 publications

Endogenous oxidized DNA bases and APE1 regulate the formation of G-quadruplex structures in the genome

Endogenous oxidized DNA bases and APE1 regulate the formation of G-quadruplex structures in the genome

Thermodynamic characterization and nearest neighbor parameters for RNA duplexes under molecular crowding conditions

Bacterial Ligase D preternary-precatalytic complex performs efficient abasic sites processing at double strand breaks during nonhomologous end joining

Contact Info

Product

Resources

About