Evidence map›Paper›PMID 31740608›Full record

ArticleProceedings of the National Academy of Sciences of the United States of America2019

Structures and single-molecule analysis of bacterial motor nuclease AdnAB illuminate the mechanism of DNA double-strand break resection.

Ning Jia, Mihaela C Unciuleac, Chaoyou Xue, Eric C Greene, Dinshaw J Patel, Stewart Shuman

Abstract read
In one paragraph

Article in Proceedings of the National Academy of Sciences of the United States of America, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 13 papers.

0numbers the graph read from it
0cells of the map it votes in
13citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

13 citing papers in PubMed.

  1. Article
  2. Article
  3. Article
  4. Article
  5. RecBCD enzyme: mechanistic insights from mutants of a complex helicase-nuclease.Microbiology and molecular biology reviews : MMBR · 2023
    Review
  6. Article
  7. Article
  8. Article
  9. Review
  10. Article
  11. Review
  12. Clutch mechanism of chemomechanical coupling in a DNA resecting motor nuclease.Proceedings of the National Academy of Sciences of the United States of America · 2021
    Article
  13. Review
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

6 authors.

Ning JiaStructural Biology Program, Sloan Kettering Institute, New York, NY 10065.
Mihaela C UnciuleacMolecular Biology Program, Sloan Kettering Institute, New York, NY 10065.
Chaoyou XueDepartment of Biochemistry and Molecular Biophysics, Columbia University, New York, NY 10032.
Eric C GreeneDepartment of Biochemistry and Molecular Biophysics, Columbia University, New York, NY 10032.
Dinshaw J PatelStructural Biology Program, Sloan Kettering Institute, New York, NY 10065; pateld@mskcc.org s-shuman@ski.mskcc.org.
Stewart ShumanMolecular Biology Program, Sloan Kettering Institute, New York, NY 10065; pateld@mskcc.org s-shuman@ski.mskcc.org.ORCID 0000-0001-5034-6438

Funding

X-RAY CRYSTALLOGRAPHYP30CA008748 · NCI · SLOAN-KETTERING INSTITUTE FOR CANCER RES · PI Hongbiao Carl Lekaye · 1985 to 2026
$347.4M
Novel pathway of DNA inter-strand crosslink repair in mycobacteriaR01AI064693 · NIAID · SLOAN-KETTERING INSTITUTE FOR CANCER RES · PI Michael S Glickman, Stewart H Shuman · 2005 to 2026
$11.1M
Mechanisms of DNA and RNA TransactionsR35GM126945 · NIGMS · SLOAN-KETTERING INST CAN RESEARCH · PI Stewart H Shuman · 2018 to 2026
$8.9M
Protein purification instrumentation in support of single molecule studies of genome integrityR35GM118026 · NIGMS · COLUMBIA UNIVERSITY HEALTH SCIENCES · PI GREENE, ERIC C · 2016 to 2025
$5.7M
NCI NIH HHS P30 CA008748NIAID NIH HHS R01 AI064693NIGMS NIH HHS R35 GM118026NIGMS NIH HHS R35 GM126945
6 · The paper itself

Abstract

Mycobacterial AdnAB is a heterodimeric helicase-nuclease that initiates homologous recombination by resecting DNA double-strand breaks (DSBs). The AdnA and AdnB subunits are each composed of an N-terminal motor domain and a C-terminal nuclease domain. Here we report cryoelectron microscopy (cryo-EM) structures of AdnAB in three functional states: in the absence of DNA and in complex with forked duplex DNAs before and after cleavage of the 5' single-strand DNA (ssDNA) tail by the AdnA nuclease. The structures reveal the path of the 5' ssDNA through the AdnA nuclease domain and the mechanism of 5' strand cleavage; the path of the 3' tracking strand through the AdnB motor and the DNA contacts that couple ATP hydrolysis to mechanical work; the position of the AdnA iron-sulfur cluster subdomain at the Y junction and its likely role in maintaining the split trajectories of the unwound 5' and 3' strands. Single-molecule DNA curtain analysis of DSB resection reveals that AdnAB is highly processive but prone to spontaneous pausing at random sites on duplex DNA. A striking property of AdnAB is that the velocity of DSB resection slows after the enzyme experiences a spontaneous pause. Our results highlight shared as well as distinctive properties of AdnAB vis-à-vis the RecBCD and AddAB clades of bacterial DSB-resecting motor nucleases.

Indexed as

DNA Breaks, Double-StrandedAdenosine TriphosphateAdenylyl ImidodiphosphateBacterial ProteinsBinding SitesCatalytic DomainCryoelectron MicroscopyDNA, Single-StrandedEndodeoxyribonucleasesHydrolysisIron-Sulfur ProteinsModels, MolecularMutationMycobacterium smegmatisNucleic Acid HeteroduplexesProtein DomainsAdenosine TriphosphateAdenylyl ImidodiphosphateBacterial ProteinsDNA, Single-StrandedEndodeoxyribonucleasesIron-Sulfur ProteinsNucleic Acid Heteroduplexescryoelectron microscopyDNA curtainDNA end resectionhomologous recombination

Identifiers

PMID31740608
PMCPMC6900545

What OpenQuestion holds

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Registered trials

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.