Journal: Biochemistry and Biophysics Reports

Article Title: Mechanisms of search for specific sites in DNA by DNA-binding proteins

doi: 10.1016/j.bbrep.2026.102604

Figure Lengend Snippet: A. Model for the search by the Fpg enzyme for damage in DNA . The enzyme moves along the DNA helix during active or nonspecific search. B . Model of the structure of the protein-nucleic acid complex during damage search, by intercalation of an aromatic amino acid residue (indicated in red) or without incorporation into the DNA double helix (residue indicated in blue). (Reprinted by permission from Oxford University Press: [Nucleic Acids Res.] Dunn A. R., Kad N. M., Nelson S. R., Warshaw D. M., Wallace S. S. Nucleic Acids Res. 2011. V. 39, № 17. P. 7487-7498, copyright 2011).

Article Snippet: Its insertion into the DNA double helix "switches" the enzyme from the fast sliding phase in the form of a collision complex to the phase of active search for damage in the DNA double helix, with the phenylalanine residue playing the role of a sensor to help detect the oxidized base in the DNA double helix [ , ].

Techniques: Residue

Journal: bioRxiv

Article Title: Diversity and Genomic Organization of Non-B DNA Motifs in Haplotype-Resolved Human Genome Assemblies

doi: 10.64898/2026.03.05.709836

Figure Lengend Snippet: (A) Cohort composition of 65 diploid individuals spanning five continental superpopulations (African, East Asian, American, European, South Asian), with haplotype-resolved assemblies generated for each individual by the HGSVC. Haplotype-specific BAMs aligned to GRCh38 and T2T-CHM13v2.0 were split by chromosome and converted to FASTA for computational non-B DNA motif annotation. Two tools were applied: non-B gfa for broad motif classes and Quadron for G-Quadruplexes. Non-B DNA motif classes include Z-DNA, inverted repeats (cruciform DNA), mirror repeats (H-DNA), direct repeats, A-phased repeats, and G-Quadruplexes. (B) Cumulative non-B DNA coverage across haplotypes in autosomes and sex chromosomes, stratified by reference genome (GRCh38 vs T2T-CHM13v2.0) and haplotype (1 vs 2). Coverage is reported as the summed base-pair span of annotated motifs across all haplotypes. (C) Percentage of genome covered by distinct non-B DNA classes in haplotype-resolved assemblies aligned to T2T-CHM13v2.0 (blue) and GRCh38 (red). Motif types include inverted repeats (IR), mirror repeats (MR), direct repeats (DR), A-phased repeats (APR), Z-DNA (Z), and G-quadruplexes (G4). (D) Chromosomal ideograms of motifs recurrently annotated in five or more haplotypes aligned to CHM13. Odds ratios for G4s and IRs in CpG islands highlight the enrichment of G4s in these regions (1.517) and depletion of IRs in these regions (0.617). (E) Population-level comparisons of non-B DNA coverage. Per-haplotype base-pair coverage of inverted repeats (IRs) is significantly higher in African (AFR) haplotypes compared to non-African Haplotypes (Mann-Whitney U test, p < 0.001), while no significant difference is observed for positive-strand G-quadruplexes (NS).

Article Snippet: These repetitive sequences include non-B DNA (nBDNA) motifs, which have the unique ability to adopt DNA conformations distinct from the canonical right-handed B-form double helix ( , ).

Techniques: Generated, MANN-WHITNEY

Journal: bioRxiv

Article Title: Diversity and Genomic Organization of Non-B DNA Motifs in Haplotype-Resolved Human Genome Assemblies

doi: 10.64898/2026.03.05.709836

Figure Lengend Snippet: (A) Fraction of total centromeric sequence (left) and active α-satellite higher-order repeat (HOR) arrays (right) covered by major non-B DNA motif classes across haplotypes. Inverted repeats (IRs) represent the largest fraction of centromeric and HOR-array sequence, followed by direct repeats (DRs) and mirror repeats (MRs), whereas G4 and Z-DNA motifs are comparatively rare. (B) Median log odds ratios of non-B DNA motif enrichment within CENP-B boxes across haplotypes for chromosomes 1, 11, 12, and 15. Chromosome-specific enrichments include IRs in CENP-B boxes on chromosome 11, and A-phased repeats (APRs) in CENP-B boxes on chromosomes 1 and 15 (C) Enrichment of non-B DNA motifs across CENP-B monomer-spacing categories (1-10+ monomers) for representative centromeres on chromosomes 3 and 11. Certain motifs display spacing-dependent enrichments, including Z-DNA on chromosome 3 and APRs on chromosome 11. (D) Normalized density profiles of inverted repeats (IRs) and Z-DNA motifs across chromosome 3 centromeres (scaled position 0-1), separated by population group. Both African (AFR) and American (AMR) haplotypes show peaks aligned with α-satellite HOR arrays, though with notable differences in positional organization. (E-F) Representative chromosome 3 centromeres from samples NA19437 (AFR) and HG00731 (AMR), showing motif-density tracks for Z-DNA, IRs, DRs, MRs, and APRs across the α-satellite HOR array.

Article Snippet: These repetitive sequences include non-B DNA (nBDNA) motifs, which have the unique ability to adopt DNA conformations distinct from the canonical right-handed B-form double helix ( , ).

Techniques: Sequencing

Journal: bioRxiv

Article Title: Diversity and Genomic Organization of Non-B DNA Motifs in Haplotype-Resolved Human Genome Assemblies

doi: 10.64898/2026.03.05.709836

Figure Lengend Snippet: (A) Genome-wide enrichment of non-B DNA motif classes within intrachromosomal and inter-chromosomal SDs relative to the genome background. Direct repeats (DRs) exhibit the strongest enrichment in both SD types, followed by G4 and APR motifs, with different enrichment distributions between intra- and inter-chromosomal duplications. Z-DNA, inverted repeats (IRs), and mirror repeats (MRs) show no enrichment (log odds ratio = 0, Fisher’s exact test). (B) Stability-stratified enrichment of G-quadruplex (G4) motifs within SDs, showing that both stable and unstable G4s are enriched relative to genome background, with unstable G4s displaying slightly higher enrichment in both SD types. (C) Stability-stratified enrichment of inverted repeat motifs within SDs. Although IRs as a class are not strongly enriched within SDs (log odds ratios close to 0), stable IRs consistently show higher odds ratios than unstable IRs in both intra- and inter-chromosomal SDs, indicating a relative preference for more stable IR configurations within duplicated regions. (D) Chromosome-resolved enrichment of DR, G4, and APR motifs within fixed SDs. Inter-chromosomal SDs show strong DR and APR enrichment on chromosomes 1, 9, and 17, whereas intrachromosomal SDs show elevated G4 enrichment on chromosome 12 and along chromosome 19. (E-F) Representative density ideograms illustrating spatial distributions of enriched motifs within SDs. DRs are prominent in pericentromeric inter-chromosomal SDs on chromosomes 1 and 9, while G4s show higher density within intrachromosomal SDs on the short arm of chromosome 12 and across gene-rich regions of chromosome 19.

Article Snippet: These repetitive sequences include non-B DNA (nBDNA) motifs, which have the unique ability to adopt DNA conformations distinct from the canonical right-handed B-form double helix ( , ).

Techniques: Genome Wide

Journal: bioRxiv

Article Title: Diversity and Genomic Organization of Non-B DNA Motifs in Haplotype-Resolved Human Genome Assemblies

doi: 10.64898/2026.03.05.709836

Figure Lengend Snippet: (A) Kernel density estimates (KDE) of six non-B DNA motif classes across ± 2kb surrounding insertion breakpoints. Multiple motif types show pronounced clustering at breakpoint positions, with the strongest peaks observed for mirror repeats (MRs) and direct repeats (DRs). (B) Average free energy profiles of inverted repeats in the 2 kb pre- and post-flanking regions of insertions, showing increasing IR stability as the breakpoint is approached, followed by a sharp local destabilization at the breakpoint. (C) Average stability (Quadron Q-scores) of G-quadruplex (G4) motifs across insertion flanking regions, demonstrating progressively higher G4 stability near breakpoints. (D) Schematic overview of the breakpoint-centered flanking-sequence analysis used to quantify local homology and non-B motif content across insertion classes. (E) Cumulative distribution functions (CDFs) of local BLAST alignment (left) and inverted repeat coverage (right) in insertion flanks from GRCh38 and T2T-CHM13 assemblies, stratified by insertion length (short, medium, long). (F) log odds ratios (Fisher’s exact test) for G4 and IR enrichment within insertions and deletions overlapping fixed intrachromosomal and inter-chromosomal segmental duplications (SDs).

Article Snippet: These repetitive sequences include non-B DNA (nBDNA) motifs, which have the unique ability to adopt DNA conformations distinct from the canonical right-handed B-form double helix ( , ).

Techniques: Sequencing

Journal: bioRxiv

Article Title: Diversity and Genomic Organization of Non-B DNA Motifs in Haplotype-Resolved Human Genome Assemblies

doi: 10.64898/2026.03.05.709836

Figure Lengend Snippet: (A) Average number of bases covered by each non-B DNA motif class within LINE/L1 SINE/AU, and Retroposon/SVA insertions. Retroposon/SVA elements display the highest overall motif coverage across all motif types. (B) Distribution of G4 stability (Quadron Q-score) across MEI families. Retroposon/SVA insertions harbour significantly more stable G4s than LINE/L1 and SINE/Alu elements (Mann-Whitney U, p < 0.001). (C) Free energy distributions of inverted repeats (IRs) across MEI classes, showing that SVA elements contain the most stable IR structures relative to other MEIs elements (Mann-Whitney U, p < 0.001). (D) Stability profiles of G4 motifs across SVA subfamilies (A-F), revealing that evolutionarily younger subfamilies (D-F) contain G4s with the highest predicted stability, whereas older families show lower and more variable stability. (E) UpSet plot showing recurrent combinations of co-occurring non-B DNA motifs within SVA elements. A total of 722 SVAs contain DR, MR, IR, and G4 motifs, the most common motif combination observed genome wide. (F) Normalized positional density of non-B DNA motifs along the canonical SVA structure. DR and MR motifs are enriched toward the 5’ and 3’ ends, while G4 and IR motifs are concentrated within the central FC-rich VNTR domain, with an additional small G4 peak in the CCCTCT-rich 5’ region. (G) Representative example of an SVA-F insertion at the A4GNT locus (present in 75 haplotypes), illustrating the dense clustering of motifs within an individual SVA.

Article Snippet: These repetitive sequences include non-B DNA (nBDNA) motifs, which have the unique ability to adopt DNA conformations distinct from the canonical right-handed B-form double helix ( , ).

Techniques: MANN-WHITNEY, Genome Wide