Hou P et al., PNAS - This study combines kinetic assays and X‑ray crystallography to show how 8‑oxo‑guanosine triphosphate (8‑oxo‑rGTP) is incorporated by RNA polymerase II and how its pairing geometry with template bases (dC vs dA) differentially alters incorporation efficiency, extension, and proofreading, thereby introducing transcription‑coupled RNA damage. Key terms: RNA damage, 8-oxo-rGTP, RNA polymerase II, transcription fidelity, oxidative stress.

Study Highlights:
Pol II incorporates 8‑oxo‑rGTP efficiently opposite dC with kinetics comparable to GTP, whereas incorporation opposite dA is much slower but ~150‑fold more efficient than misincorporation of undamaged rGTP. Extension proceeds rapidly from a 3′‑r8OG:dC pair but is markedly slower from a 3′‑r8OG:dA pair. TFIIS‑stimulated proofreading cleaves r8OG:dC robustly but r8OG:dA is resistant to backtracking and cleavage. Crystal structures reveal 8‑oxo‑rG adopts anti Watson–Crick geometry with dC in the A‑site but flips to syn Hoogsteen geometry with dA, where an interaction with Rpb2 E529 stabilizes a pretranslocation state.

Conclusion:
Oxidation of the nucleotide pool can directly undermine Pol II fidelity by enabling efficient incorporation and differential handling of 8‑oxo‑rGTP, producing transcription‑coupled RNA damage with potential consequences for RNA processing, translation, and disease.

Music:
Enjoy the music based on this article at the end of the episode.

Article title:
Structural basis of transcription -coupled RNA damage by incorporation of oxidized ribonucleotides

First author:
Hou P

Journal:
PNAS

DOI:
10.1073/pnas.2602266123

Reference:
Hou P, Lee C, Chong J, Oh J, Wang D. Structural basis of transcription-coupled RNA damage by incorporation of oxidized ribonucleotides. PNAS. 2026;123(16):e2602266123. doi:10.1073/pnas.2602266123

License:
This episode is based on an open-access article published under the Creative Commons Attribution 4.0 International License (CC BY 4.0) – https://creativecommons.org/licenses/by/4.0/

Support:
Base by Base – Stripe donations: https://donate.stripe.com/7sY4gz71B2sN3RWac5gEg00

Official website https://basebybase.com

On PaperCast Base by Base you'll discover the latest in genomics, functional genomics, structural genomics, and proteomics.

Episode link: https://basebybase.com/episodes/8oxo-rgpt-transcription-rna-damage

QC:
This episode was checked against the original article PDF and publication metadata for the episode release published on 2026-04-24.

QC Scope:
- article metadata and core scientific claims from the narration
- excludes analogies, intro/outro, and music
- transcript coverage: Audited sections on background, kinetic experiments, structural determinations, proofreading, translocation mechanics, and disease relevance; aligned with the canonical article.
- transcript topics: Oxidative stress and oxidized ribonucleotides; 8-oxo-rGTP incorporation opposite dC and dA templates; Presteady-state kinetics and incorporation efficiency; Extension after 8-oxo-rGTP incorporation; TFIIS proofreading and backtracking with oxidized nucleotides; Structural basis: A-site anti conformation with dC; syn Hoogsteen with dA; E529 fork loop 2 interaction

QC Summary:
- factual score: 10/10
- metadata score: 10/10
- supported core claims: 8
- claims flagged for review: 0
- metadata checks passed: 4
- metadata issues found: 0

Metadata Audited:
- article_doi
- article_title
- article_journal
- license

Factual Items Audited:
- 8-oxo-rGTP can be efficiently incorporated opposite dC, with efficiency comparable to GTP
- 8-oxo-rGTP opposite dA is misincorporated ~150-fold more efficiently than rGTP misincorporation
- Pol II extends more efficiently from 8-oxo-rG:d...

Wang Y et al et al., PNAS - This episode covers a PNAS study describing v96, a personalized plasma cell-free DNA assay that tracks up to 96 patient-specific mutations to sensitively quantify measurable residual disease (MRD) in AML patients before and after allogeneic hematopoietic cell transplantation. Key terms: cell-free DNA, measurable residual disease, acute myeloid leukemia, hematopoietic cell transplantation, duplex sequencing.

Study Highlights:
The personalized v96 assay detected residual leukemia in 100% of 30 AML patients at clinical remission, compared with 20% by flow cytometry. Plasma cfDNA was more informative and sensitive than bone marrow DNA and driver mutation assays, with 90% of patients positive at 2 months posttransplant. Higher pretransplant mutant molecule counts correlated with relapse risk, and leukemic burden typically fell only after immunosuppression was discontinued, consistent with a graft-versus-leukemia effect.

Conclusion:
A plasma-based multiplexed assay (v96) enables highly sensitive, noninvasive MRD monitoring in AML patients undergoing transplantation and may inform timing of immunosuppression and posttransplant interventions, though larger studies are needed to confirm clinical utility.

Music:
Enjoy the music based on this article at the end of the episode.

Article title:
A plasma - based DNA test for quantification of disease burden in acute myeloid leukemia patients undergoing bone marrow transplantation

First author:
Wang Y et al

Journal:
PNAS

DOI:
10.1073/pnas.2537987123

Reference:
Wang Y et al., A plasma-based DNA test for quantification of disease burden in acute myeloid leukemia patients undergoing bone marrow transplantation. PNAS. 2026;123(16):e2537987123. doi:10.1073/pnas.2537987123

License:
This episode is based on an open-access article published under the Creative Commons Attribution 4.0 International License (CC BY 4.0) – https://creativecommons.org/licenses/by/4.0/

Support:
Base by Base – Stripe donations: https://donate.stripe.com/7sY4gz71B2sN3RWac5gEg00

Official website https://basebybase.com

On PaperCast Base by Base you'll discover the latest in genomics, functional genomics, structural genomics, and proteomics.

Episode link: https://basebybase.com/episodes/v96-plasma-ctdna-aml-transplant

QC:
This episode was checked against the original article PDF and publication metadata for the episode release published on 2026-04-21.

QC Scope:
- article metadata and core scientific claims from the narration
- excludes analogies, intro/outro, and music
- transcript coverage: Audited the transcript’s presentation of the v96 methodology, passenger vs driver mutations, plasma vs marrow MRD detection, relapse prediction, and posttransplant immunosuppression dynamics against the original article.
- transcript topics: v96 workflow and passenger mutation panel; duplex sequencing (SaferSeqS) and error suppression; plasma vs bone marrow cell-free DNA for MRD detection; driver vs passenger mutations for MRD assessment; predictive power for relapse (352-fold difference pre-transplant); graft-versus-leukemia (GvL) dynamics and immunosuppression

QC Summary:
- factual score: 10/10
- metadata score: 10/10
- supported core claims: 5
- claims flagged for review: 0
- metadata checks passed: 4
- metadata issues found: 0

Metadata Audited:
- article_doi
- article_title
- article_journal
- license

Factual Items Audited:
- v96 assay tracks up to 96 leukemia-specific passenger mutations in plasma cfDNA and detects residual leukemia in all patients at complete remission (CR) by v96, vs 20% by flow cyto
- plasma cfDNA mutant-allele fractions (MAF) are higher than bone marrow DNA (2.9% vs 0.42%) at CR
- pre-transplant plasma mutant m...

• (00:00:09) - How to Catch a Leukemia Patient's Disease in the Dark
• (00:06:43) - The 96-Point mutation detection
• (00:11:15) - Blood tests for leukemia no longer find cancer
• (00:14:04) - Can V96 Predict Who Will Get Sick?
• (00:20:53) - 96 Names in the Line

Holta KB et al., Proceedings of the National Academy of Sciences (PNAS) - This episode explains a quantitative framework for diffusion on spatially embedded dynamic mitochondrial networks. The study combines analytic theory, agent-based simulations, and live-cell imaging to show how connectivity, fusion/fission, and mobility set biomolecular mixing on mitochondrial populations. Key terms: mitochondria, diffusion, intracellular transport, temporal networks, fusion-fission.

Study Highlights:
The authors develop an analytic and simulation framework for diffusive spreading on spatially embedded dynamic networks formed by mitochondrial fusion and fission. They identify a connectivity-driven transition from three-dimensional dispersion across transiently interacting clusters (social regime) to low-dimensional transport along largely stationary interconnected tubules (physical regime). The steady-state distribution is determined by competing timescales for cluster filling, encounter, fusion/fission, and material decay. Application to three human cell lines reveals cell-type variability in predicted spreading times, with hyperfused networks limited by intracluster diffusion and fragmented networks limited by encounters.

Conclusion:
Network connectivity and the balance of diffusion, encounter, and fusion/fission timescales quantitatively determine mitochondrial material homogenization, producing distinct scaling regimes with measurable predictions across cell types.

Music:
Enjoy the music based on this article at the end of the episode.

Article title:
Diffusive spreading across dynamic mitochondrial network architectures

First author:
Holta KB

Journal:
Proceedings of the National Academy of Sciences (PNAS)

DOI:
10.1073/pnas.2523913123

Reference:
Holta KB, Zurita C, Teryoshin L, Lewis SC, Koslover EF. Diffusive spreading across dynamic mitochondrial network architectures. Proc Natl Acad Sci U S A. 2026;123(15):e2523913123. doi:10.1073/pnas.2523913123

License:
This episode is based on an open-access article published under the Creative Commons Attribution 4.0 International License (CC BY 4.0) – https://creativecommons.org/licenses/by/4.0/

Support:
Base by Base – Stripe donations: https://donate.stripe.com/7sY4gz71B2sN3RWac5gEg00

Official website https://basebybase.com

On PaperCast Base by Base you'll discover the latest in genomics, functional genomics, structural genomics, and proteomics.

Episode link: https://basebybase.com/episodes/diffusive-spreading-mitochondrial-networks

QC:
This episode was checked against the original article PDF and publication metadata for the episode release published on 2026-04-19.

QC Scope:
- article metadata and core scientific claims from the narration
- excludes analogies, intro/outro, and music
- transcript coverage: Substantive auditing of the transcript’s representation of the article’s core framework, regimes, timescales, cell-type predictions, modeling approach, and acknowledged limitations, with cross-checks against the original article text and the facts pack.
- transcript topics: Temporal networks framework for diffusion on dynamic mitochondrial networks; Physical vs social mitochondrial network regimes; Four timescales governing diffusion: decay, cluster filling, encounter, fission; Agent-based spherocylindrical model and finite-volume diffusion; Time-resolved imaging and cell-type parameterization (SH-SY5Y, IMR90, U2OS); Predictions of spreading times across cell types

QC Summary:
- factual score: 10/10
- metadata score: 10/10
- supported core claims: 7
- claims flagged for review: 0
- metadata checks passed: 4
- metadata issues found: 0

Metadata Audited:
- article_doi
- article_title
- article_journal
- license

Factual Items Audite...