Evidence map›Paper›PMID 28919440›Full record

ArticleStructure (London, England : 1993)2017

Structural Insight into BLM Recognition by TopBP1.

Luxin Sun, Yuhao Huang, Ross A Edwards, Sukmin Yang, Andrew N Blackford, Wojciech Niedzwiedz, J N Mark Glover

Open access · bronzeAbstract read
In one paragraph

Article in Structure (London, England : 1993), 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 21 papers.

0numbers the graph read from it
0cells of the map it votes in
21citing papers in PubMed
1.3field-weighted citation impact, top 19% of its field
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

21 citing papers in PubMed, 30 citations in OpenAlex.

  1. Article
  2. Article
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  5. Pre-rRNA Facilitates TopBP1-Mediated DNA Double-Strand Break Response.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2023
    Article
  6. Review
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  8. Review
  9. InInternational journal of molecular sciences · 2021
    Article
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4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

7 authors at 3 institutions in 2 countries.

Luxin SunDepartment of Biochemistry, University of Alberta, Edmonton, AB T6G 2H7, Canada.
Yuhao HuangDepartment of Biochemistry, University of Alberta, Edmonton, AB T6G 2H7, Canada.
Ross A EdwardsDepartment of Biochemistry, University of Alberta, Edmonton, AB T6G 2H7, Canada.
Sukmin YangDepartment of Biochemistry, University of Alberta, Edmonton, AB T6G 2H7, Canada.
Andrew N BlackfordDepartment of Oncology, Weatherall Institute of Molecular Medicine, University of Oxford, John Radcliffe Hospital, Oxford OX3 9DS, UK; Cancer Research UK and Medical Research Council Oxford Institute for Radiation Oncology, University of Oxford, Oxford OX3 7DQ, UK.
Wojciech NiedzwiedzDepartment of Oncology, Weatherall Institute of Molecular Medicine, University of Oxford, John Radcliffe Hospital, Oxford OX3 9DS, UK.
J N Mark GloverDepartment of Biochemistry, University of Alberta, Edmonton, AB T6G 2H7, Canada. Electronic address: mark.glover@ualberta.ca.
University of Alberta · CACancer Research UK · GBJohn Radcliffe Hospital · GB

Funding

Transcription-Coupled & Replication-Associated Excision RepairP01CA092584 · NCI · UNIVERSITY OF CALIF-LAWRENC BERKELEY LAB · PI John A. Tainer · 2001 to 2026
$89.6M
Cancer Research UK 20772Cancer Research UK C29215/A20772NCI NIH HHS P01 CA092584
6 · The paper itself

Abstract

Topoisomerase IIβ binding protein 1 (TopBP1) is a critical protein-protein interaction hub in DNA replication checkpoint control. It was proposed that TopBP1 BRCT5 interacts with Bloom syndrome helicase (BLM) to regulate genome stability through either phospho-Ser304 or phospho-Ser338 of BLM. Here we show that TopBP1 BRCT5 specifically interacts with the BLM region surrounding pSer304, not pSer338. Our crystal structure of TopBP1 BRCT4/5 bound to BLM reveals recognition of pSer304 by a conserved pSer-binding pocket, and interactions between an FVPP motif N-terminal to pSer304 and a hydrophobic groove on BRCT5. This interaction utilizes the same surface of BRCT5 that recognizes the DNA damage mediator, MDC1; however the binding orientations of MDC1 and BLM are reversed. While the MDC1 interactions are largely electrostatic, the interaction with BLM has higher affinity and relies on a mix of electrostatics and hydrophobicity. We suggest that similar evolutionarily conserved interactions may govern interactions between TopBP1 and 53BP1.

Indexed as

AnimalsBinding SitesCarrier ProteinsCrystallography, X-RayDNA-Binding ProteinsHumansMiceModels, MolecularNuclear ProteinsPhosphorylationProtein ConformationRecQ HelicasesSerineTrans-ActivatorsBloom syndrome proteinCarrier ProteinsDNA-Binding ProteinsNuclear ProteinsRecQ HelicasesSerineTOPBP1 protein, humanTopbp1 protein, mouseTrans-ActivatorsBLMBloom syndromeBRCTfluorescence polarizationphosphopeptide interactionsTopBP1X-ray crystallography

Identifiers

PMID28919440
PMCPMC6044410
OpenAlexW2755190636

What OpenQuestion holds

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Read underepoch 390

Registered trials

None linked

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.