6XAH

Structure of a Stable Interstrand DNA Crosslink Involving an dA Amino Group and an Abasic Site

Summary for 6XAH

• Entry DOI: 10.2210/pdb6xah/pdb
• NMR Information: BMRB: 30759
• Descriptor: DNA (5'-D(*TP*AP*TP*GP*TP*CP*TP*AP*AP*GP*TP*TP*CP*AP*TP*CP*TP*A)-3'), DNA (5'-D(*TP*AP*GP*AP*TP*GP*AP*AP*CP*(AAB)P*TP*AP*GP*AP*CP*AP*TP*A)-3') (2 entities in total)
• Functional Keywords: interstrand crosslink, ap site, dna
• Biological source: Homo sapiens (Human); More
• Total number of polymer chains: 2
• Total formula weight: 10920.12

Authors

Kellum Jr., A.H.,Qiu, D.,Voehler, M.W.,Martin, W.J.,Gates, K.S.,Stone, M.P. (deposition date: 2020-06-04, release date: 2021-05-05, Last modification date: 2024-05-01)

Primary citation

Kellum Jr., A.H.,Qiu, D.Y.,Voehler, M.W.,Martin, W.,Gates, K.S.,Stone, M.P.
Structure of a Stable Interstrand DNA Cross-Link Involving a beta- N -Glycosyl Linkage Between an N 6 -dA Amino Group and an Abasic Site.
Biochemistry, 60:41-52, 2021

PubMed Abstract: Abasic (AP) sites are one of the most common forms of DNA damage. The deoxyribose ring of AP sites undergoes anomerization between α and β configurations, via an electrophilic aldehyde intermediate. In sequences where an adenine residue is located on the opposing strand and offset 1 nt to the 3' side of the AP site, the nucleophilic -dA amino group can react with the AP aldehyde residue to form an interstrand cross-link (ICL). Here, we present an experimentally determined structure of the dA-AP ICL by NMR spectroscopy. The ICL was constructed in the oligodeoxynucleotide 5'-d(TATGTCTAAGTTCATCTA)-3':5'-d(TAGATGAACXTAGACATA)-3' (X=AP site), with the dA-AP ICL forming between A and X. The NMR spectra indicated an ordered structure for the cross-linked DNA duplex and afforded detailed spectroscopic resonance assignments. Structural refinement, using molecular dynamics calculations restrained by NOE data (rMD), revealed the structure of the ICL. In the dA-AP ICL, the 2'-deoxyribosyl ring of the AP site was ring-closed and in the β configuration. Juxtapositioning the -dA amino group and the aldehydic C1 of the AP site within bonding distance while simultaneously maintaining two flanking unpaired A and T bases stacked within the DNA is accomplished by the unwinding of the DNA at the ICL. The structural data is discussed in the context of recent studies describing the replication-dependent unhooking of the dA-AP ICL by the base excision repair glycosylase NEIL3.

PubMed: 33382597
DOI: 10.1021/acs.biochem.0c00596

Experimental method

SOLUTION NMR