Evidence map›Paper›PMID 27924004›Full record

ArticleNucleic acids research2017

Temporal association of ORCA/LRWD1 to late-firing origins during G1 dictates heterochromatin replication and organization.

Yating Wang, Abid Khan, Anna B Marks, Owen K Smith, Sumanprava Giri, Yo-Chuen Lin, Rachel Creager, David M MacAlpine, Kannanganattu V Prasanth, Mirit I Aladjem and 1 more

Open access · goldAbstract read
In one paragraph

Article in Nucleic acids research, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 33 papers.

0numbers the graph read from it
0cells of the map it votes in
33citing papers in PubMed
2.6field-weighted citation impact, top 10% 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

33 citing papers in PubMed, 51 citations in OpenAlex.

  1. Article
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  5. Article
  6. Article
  7. Article
  8. Article
  9. Review
  10. Article
  11. Review
  12. Article
  13. ORChestra coordinates the replication and repair music.BioEssays : news and reviews in molecular, cellular and developmental biology · 2023
    Article
  14. Article
  15. DNA replication timing: Biochemical mechanisms and biological significance.BioEssays : news and reviews in molecular, cellular and developmental biology · 2022
    Article
  16. Article
  17. Article
  18. Review
  19. Review
  20. Article
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

11 authors at 3 institutions in 1 country.

Yating WangDepartment of Cell and Developmental Biology, University of Illinois at Urbana-Champaign, 601S Goodwin Avenue, Urbana, IL 61801, USA.
Abid KhanDepartment of Cell and Developmental Biology, University of Illinois at Urbana-Champaign, 601S Goodwin Avenue, Urbana, IL 61801, USA.
Anna B MarksDevelopmental Therapeutics Branch, Center for Cancer Research, NCI, NIH, Bethesda, MD 20892, USA.
Owen K SmithDevelopmental Therapeutics Branch, Center for Cancer Research, NCI, NIH, Bethesda, MD 20892, USA.
Sumanprava GiriDepartment of Cell and Developmental Biology, University of Illinois at Urbana-Champaign, 601S Goodwin Avenue, Urbana, IL 61801, USA.
Yo-Chuen LinDepartment of Cell and Developmental Biology, University of Illinois at Urbana-Champaign, 601S Goodwin Avenue, Urbana, IL 61801, USA.
Rachel CreagerDepartment of Pharmacology and Cancer Biology, Duke University School of Medicine, Durham, NC 27710, USA.
David M MacAlpineDepartment of Pharmacology and Cancer Biology, Duke University School of Medicine, Durham, NC 27710, USA.
Kannanganattu V PrasanthDepartment of Cell and Developmental Biology, University of Illinois at Urbana-Champaign, 601S Goodwin Avenue, Urbana, IL 61801, USA.
Mirit I AladjemDevelopmental Therapeutics Branch, Center for Cancer Research, NCI, NIH, Bethesda, MD 20892, USA.
Supriya G PrasanthDepartment of Cell and Developmental Biology, University of Illinois at Urbana-Champaign, 601S Goodwin Avenue, Urbana, IL 61801, USA.
University of Illinois Urbana-Champaign · USCenter for Cancer Research · USDuke University · US

Funding

Initiation of DNA Replication in Mammalian CellsZIABC010411 · NCI · DIVISION OF BASIC SCIENCES - NCI · PI ALADJEM, MIRIT · 2009 to 2025
$25.0M
Characterization of nuclear retained RNA-mediated gene regulatory mechanismR01GM088252 · NIGMS · UNIVERSITY OF ILLINOIS AT URBANA-CHAMPAIGN · PI KANNANGANATTU, PRASANTH KUMAR VIJAYAN · 2011 to 2015
$1.4M
Role of ORCA in DNA replicationR01GM099669 · NIGMS · UNIVERSITY OF ILLINOIS AT URBANA-CHAMPAIGN · PI PRASANTH, SUPRIYA G · 2012 to 2016
$1.3M
Chromatin architecture defines DNA replication originsR01GM104097 · NIGMS · DUKE UNIVERSITY · PI MACALPINE, DAVID M · 2013 to 2016
$1.2M
Role of ORCA in heterochromatin organization and replicationF31CA180616 · NCI · UNIVERSITY OF ILLINOIS AT URBANA-CHAMPAIGN · PI GIRI, SUMANPRAVA · 2014 to 2015
$75k
NCI NIH HHS F31 CA180616NIGMS NIH HHS R01 GM088252NIGMS NIH HHS R01 GM099669NIGMS NIH HHS R01 GM104097
6 · The paper itself

Abstract

DNA replication requires the recruitment of a pre-replication complex facilitated by Origin Recognition Complex (ORC) onto the chromatin during G1 phase of the cell cycle. The ORC-associated protein (ORCA/LRWD1) stabilizes ORC on chromatin. Here, we evaluated the genome-wide distribution of ORCA using ChIP-seq during specific time points of G1. ORCA binding sites on the G1 chromatin are dynamic and temporally regulated. ORCA association to specific genomic sites decreases as the cells progressed towards S-phase. The majority of the ORCA-bound sites represent replication origins that also associate with the repressive chromatin marks H3K9me3 and methylated-CpGs, consistent with ORCA-bound origins initiating DNA replication late in S-phase. Further, ORCA directly associates with the repressive marks and interacts with the enzymes that catalyze these marks. Regions that associate with both ORCA and H3K9me3, exhibit diminished H3K9 methylation in ORCA-depleted cells, suggesting a role for ORCA in recruiting the H3K9me3 mark at certain genomic loci. Similarly, DNA methylation is altered at ORCA-occupied sites in cells lacking ORCA. Furthermore, repressive chromatin marks influence ORCA's binding on chromatin. We propose that ORCA coordinates with the histone and DNA methylation machinery to establish a repressive chromatin environment at a subset of origins, which primes them for late replication.

Indexed as

Replication OriginBinding SitesCell LineChromatinCpG IslandsDNA (Cytosine-5-)-MethyltransferasesDNA MethylationDNA ReplicationG1 PhaseHeterochromatinHistone CodeHumansMicrotubule ProteinsChromatinDNA (Cytosine-5-)-MethyltransferasesHeterochromatinLRWD1 protein, humanMicrotubule Proteins

Identifiers

PMID27924004
PMCPMC5389698
OpenAlexW2563432555

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.