| Topic | System / study | Key quantitative findings | Core interpretation |
|---|---|---|---|
| Enzymatic reaction & domains | Human TOP2B structural/biochemical analysis | ATP-dependent strand passage: one DNA duplex (G-DNA) is transiently cleaved and a second duplex (T-DNA) is passed through the break; ATP binding/hydrolysis occurs in the N-terminal ATPase/GHKL domain; E103 is essential for ATP hydrolysis; ATPase-domain kinetics reported for ATP with Km 0.1150 mM (45–444 construct) vs 0.2670 mM and 0.1957 mM (longer constructs); CTD contains nuclear localization signals and many phosphorylation sites (pqac-00000023, pqac-00000024, pqac-00000025, pqac-00000026) | TOP2B is a nuclear type II topoisomerase whose primary substrate is duplex DNA and whose core biochemical function is ATP-coupled double-strand break/religation-mediated DNA strand passage to resolve topological stress (pqac-00000023, pqac-00000024, pqac-00000025) |
| 2024 neuronal TOP2Bcc-seq | Cultured cortical neurons; Segev et al., 2024 | Etoposide trapping: 50 μM for 30 min; TOP2Bcc-seq peaks called genome-wide: n = 35,505; correlation with prior TOP2B ChIP-seq: Spearman = 0.64; peaks relatively depleted at promoters/TSSs and enriched in gene bodies/active chromatin (pqac-00000005) | Catalytically engaged TOP2B in neurons concentrates at active gene bodies and chromatin states linked to transcription, supporting a role in managing transcription-associated torsional stress and context-specific DSB formation (pqac-00000000, pqac-00000005) |
| 2024 AD adaptive DNA-break study | Human frontal cortex nuclei; Zhang et al., 2024 | CUT&RUN sample size: AD n = 3, ND n = 3 males; AD brains had 19.9× more PAR peaks globally than ND brains; PAR-positive cells by IHC: 74.4 ± 10.5% in AD vs 16.8 ± 6.9% in ND; TOP2B-positive cells: 21.7 ± 9.3 in AD vs 82.4 ± 7.0 in ND (p < 0.05) (pqac-00000009, pqac-00000013, pqac-00000008) | AD shows a paradoxical pattern of globally increased DNA-break signal but loss of adaptive breaks at nervous-system genes, accompanied by markedly reduced TOP2B-positive cells, consistent with impaired TOP2B-linked neuronal break physiology (pqac-00000008, pqac-00000009) |
| 2024 anthracycline cardiotoxicity / iPSC-CMs | Six healthy female donor iPSC-cardiomyocyte lines; Matthews et al., 2024 | Dose-response range: 0.01–50 μM for 48 h; selected transcriptomic dose: 0.5 μM; median LD50 (μM): DOX 14.02, DNR 0.98, EPI 3.79, MTX 0.98; RNA-seq samples: 72; expressed genes analyzed: 14,084; DE genes at 3 h: DOX 19, EPI 210, DNR 532, MTX 75, TRZ 0; DE genes at 24 h: DOX 6,645, EPI 6,328, DNR 7,017, MTX 1,115, TRZ 0; TOP2B reported as essential for cardiotoxicity in mice, and TOP2i significantly decreased TOP2B and TOP2A mRNA in the model (pqac-00000021, pqac-00000016, pqac-00000019, pqac-00000015, pqac-00000020) | Anthracycline/TOP2 inhibitors trigger broad shared cardiomyocyte transcriptional responses at clinically relevant submicromolar exposure, with TOP2B implicated mechanistically in cardiotoxicity while the magnitude of transcriptional disruption varies by drug (pqac-00000016, pqac-00000019, pqac-00000021) |


*Table: This table condenses the main mechanistic and 2024 quantitative findings relevant to human TOP2B, spanning enzymology, neuronal genomic mapping, Alzheimer’s disease brain DNA-break physiology, and cardiotoxicity-related iPSC-cardiomyocyte data. It is useful as a rapid evidence summary for functional annotation and disease-context interpretation.*