Structure, function and evolution of the Helix-hairpin-Helix DNA glycosylase superfamily: Piecing together the evolutionary puzzle of DNA base damage repair mechanisms

Trasviña-Arenas, Carlos H.; Demir, Merve; Lin, Wen–Jen; David, Sheila S.

doi:10.1016/j.dnarep.2021.103231

Cited by 18 publications

(31 citation statements)

References 153 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…On a more speculative note, studies of the origin of early life on earth have shown that alpha-helical peptides can bind to DNA and synergistically regulate replication and transcription processes. [31] This observation is consistent with the idea that primordial pH oscillations or fluctuations may have influenced the transmission of genetic information. If oscillators of this type can be built from biocompatible inorganic components, then such molecular oscillations may have played a role in the formation of biological rhythms in living systems.…”

Section: Discussionsupporting

confidence: 89%

“…On a more speculative note, studies of the origin of early life on earth have shown that alpha‐helical peptides can bind to DNA and synergistically regulate replication and transcription processes [31] . This observation is consistent with the idea that primordial pH oscillations or fluctuations may have influenced the transmission of genetic information.…”

Section: Discussionsupporting

confidence: 66%

See 1 more Smart Citation

Peptide‐Modulated pH Rhythms

et al. 2022

View full text Add to dashboard Cite

Many drugs adjust and/or control the spatiotemporal dynamics of periodic processes such as heartbeat, neuronal signaling and metabolism, often by interacting with proteins or oligopeptides.Here we use a quasi-biocompatible, non-equilibrium pH oscillatory system as a biomimetic biological clock to study the effect of pH-responsive peptides on rhythm dynamics. The added peptides generate feedback that can lengthen or shorten the oscillatory period during which the peptides alternate between random coil and coiled-coil conformations. This modulation of a chemical clock supports the notion that short peptide reagents may have utility as drugs to regulate human body clocks.

show abstract

Section: Discussionsupporting

confidence: 89%

Section: Discussionsupporting

confidence: 66%

Peptide‐Modulated pH Rhythms

et al. 2022

View full text Add to dashboard Cite

show abstract

“…The first crystal structure of human NTHL1 reveals an open conformation that had not been observed previously in any of the bacterial Nth homologs, or other members of the HhH family such as OGG1 or MutY ( 69 ). In the open conformation the DNA glycosylase is catalytically inactive as the two active site residues (K220 and D239) are much too far apart, 23.5 Å, to perform a nucleophilic attack.…”

Section: Discussionmentioning

confidence: 60%

“…EcoNei has a much more dramatic 50 o interdomain rotation upon binding DNA ( 62 ). In the same H2TH family as EcoNei Neisseria meningitidis formamidopyrimidine DNA glycosylase (Fpg) was shown to undergo a 22° conformational change upon binding DNA ( 69 ). Additionally, the unliganded mammalian NEIL2 crystalized in an open conformation with a large conformational change upon binding DNA shown using small angle X-ray scattering( 68 ).…”

Section: Discussionmentioning

confidence: 99%

Caught in motion: human NTHL1 undergoes interdomain rearrangement necessary for catalysis

Carroll

Zahn

Hanley

et al. 2021

Nucleic Acids Research

View full text Add to dashboard Cite

Base excision repair (BER) is the main pathway protecting cells from the continuous damage to DNA inflicted by reactive oxygen species. BER is initiated by DNA glycosylases, each of which repairs a particular class of base damage. NTHL1, a bifunctional DNA glycosylase, possesses both glycolytic and β-lytic activities with a preference for oxidized pyrimidine substrates. Defects in human NTHL1 drive a class of polyposis colorectal cancer. We report the first X-ray crystal structure of hNTHL1, revealing an open conformation not previously observed in the bacterial orthologs. In this conformation, the six-helical barrel domain comprising the helix-hairpin-helix (HhH) DNA binding motif is tipped away from the iron sulphur cluster-containing domain, requiring a conformational change to assemble a catalytic site upon DNA binding. We found that the flexibility of hNTHL1 and its ability to adopt an open configuration can be attributed to an interdomain linker. Swapping the human linker sequence for that of Escherichia coli yielded a protein chimera that crystallized in a closed conformation and had a reduced activity on lesion-containing DNA. This large scale interdomain rearrangement during catalysis is unprecedented for a HhH superfamily DNA glycosylase and provides important insight into the molecular mechanism of hNTHL1.

show abstract

“…Even with the high precision of the polymerase during DNA replication, there is still a chance (10 –8 –10 –6 ) for each base to be replicated incorrectly at each copy, resulting in the DNA mismatch. A series of enzymes related to DNA mismatch repair (MMR) emerge during biological evolution to correct these errors. , Among the enzymes involved in DNA repair, the helix–hairpin–helix DNA glycosylase (HhH-DG) superfamily can target and repair DNA lesions with high diversity. , The defining feature of the HhH-DG superfamily is a highly conserved HhH motif followed by a Gly/Pro-rich loop and a conserved Asp residue (HhH-GPD motif) . The HhH motif is widespread in DNA-binding proteins and has been proved to be the pivotal structure for DNA binding. , …”

Section: Introductionmentioning

confidence: 99%

Functionalization of Mesoporous Silica with a G-A-Mismatched dsDNA Chain for Efficient Identification and Selective Capturing of the MutY Protein

Sun

Wang

Chen

2023

ACS Appl. Mater. Interfaces

View full text Add to dashboard Cite

MUTYH adenine DNA glycosylase and its homologous protein (collectively MutY) are typical DNA glycosylases with a [4Fe4S] cluster and a helix–hairpin–helix (HhH) motif in its structure. In the present work, the binding behaviors of the MutY protein to dsDNA containing different base mismatches were investigated. The type and distribution of base mismatch in the dsDNA chain were found to influence the DNA–protein binding interaction greatly. The [4Fe4S] cluster of the MutY protein is able to identify a G-A mismatch in the dsDNA chain specifically by monitoring the anomalies of charge transport in the dsDNA chain, allowing the entrance of the identified dsDNA chain into the internal cavity of the MutY protein and the strong DNA–protein binding at the HhH motif of the protein through multiple H-bonds. The dsDNA chain with a centrally located G-A mismatch is thus functionalized on mesoporous silica (MSN) via amination reaction, and the obtained dsDNA(G-A)@MSN is used as a powerful sorbent for the selective capturing of the MutY protein from complex samples. By using 0.5% NH3·H2O (m/v) as a stripping reagent, efficient isolation of the MutY protein from different cell lines and bacteria is achieved and the recovered MutY protein is demonstrated to maintain favorable DNA adenine glycosylase activity.

show abstract

Structure, function and evolution of the Helix-hairpin-Helix DNA glycosylase superfamily: Piecing together the evolutionary puzzle of DNA base damage repair mechanisms

Cited by 18 publications

References 153 publications

Peptide‐Modulated pH Rhythms

Peptide‐Modulated pH Rhythms

Caught in motion: human NTHL1 undergoes interdomain rearrangement necessary for catalysis

Functionalization of Mesoporous Silica with a G-A-Mismatched dsDNA Chain for Efficient Identification and Selective Capturing of the MutY Protein

Contact Info

Product

Resources

About