Evidence map›Paper›PMID 29773570›Full record

ArticleThe EMBO journal2018

hDNA2 nuclease/helicase promotes centromeric DNA replication and genome stability.

Zhengke Li, Bochao Liu, Weiwei Jin, Xiwei Wu, Mian Zhou, Vincent Zewen Liu, Ajay Goel, Zhiyuan Shen, Li Zheng, Binghui Shen

Open access · hybridAbstract read
In one paragraph

Article in The EMBO journal, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 41 papers.

0numbers the graph read from it
0cells of the map it votes in
41citing papers in PubMed
2.2field-weighted citation impact, top 11% 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

41 citing papers in PubMed, 57 citations in OpenAlex.

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  14. DNA strand breaks at centromeres: Friend or foe?Seminars in cell & developmental biology · 2024
    Review
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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

10 authors at 3 institutions in 2 countries.

Zhengke LiDepartment of Cancer Genetics and Epigenetics, Beckman Research Institute, City of Hope, Duarte, CA, USA.
Bochao LiuDepartment of Radiation Oncology, Rutgers Cancer Institute of New Jersey, Rutgers Robert Wood Johnson Medical School, Rutgers, the State University of New Jersey, New Brunswick, NJ, USA.
Weiwei JinDepartment of Cancer Genetics and Epigenetics, Beckman Research Institute, City of Hope, Duarte, CA, USA.
Xiwei WuDepartment of Molecular and Cellular Biology, Beckman Research Institute, City of Hope, Duarte, CA, USA.
Mian ZhouDepartment of Cancer Genetics and Epigenetics, Beckman Research Institute, City of Hope, Duarte, CA, USA.
Vincent Zewen LiuDepartment of Cancer Genetics and Epigenetics, Beckman Research Institute, City of Hope, Duarte, CA, USA.
Ajay GoelCenter for Gastrointestinal Research, Center for Translational Genomics and Oncology, Baylor Scott and White Research Institute and Charles A. Sammons Cancer Center, Baylor University Medical Center, Dallas, TX, USA.
Zhiyuan ShenDepartment of Radiation Oncology, Rutgers Cancer Institute of New Jersey, Rutgers Robert Wood Johnson Medical School, Rutgers, the State University of New Jersey, New Brunswick, NJ, USA.ORCID 0000-0003-2834-0309
Li ZhengDepartment of Cancer Genetics and Epigenetics, Beckman Research Institute, City of Hope, Duarte, CA, USA lzheng@coh.org bshen@coh.org.ORCID 0000-0002-3744-185X
Binghui ShenDepartment of Cancer Genetics and Epigenetics, Beckman Research Institute, City of Hope, Duarte, CA, USA lzheng@coh.org bshen@coh.org.ORCID 0000-0002-4408-407X
City of Hope · USRutgers, The State University of New Jersey · USBaylor University Medical Center · US

Funding

Transgenic Mouse FacilityP30CA033572 · NCI · CITY OF HOPE/BECKMAN RESEARCH INSTITUTE · PI STANLEY R. HAMILTON · 1985 to 2026
$86.3M
Role of Nucleases in RNA Primer Removal and MutagenesisR01CA085344 · NCI · CITY OF HOPE/BECKMAN RESEARCH INSTITUTE · PI SHEN, BINGHUI · 1999 to 2024
$7.7M
Molecular modulators of radiation-induced chromosome instability and hematopoietic damageR01CA195612 · NCI · RUTGERS BIOMEDICAL AND HEALTH SCIENCES · PI SHEN, ZHIYUAN · 2015 to 2025
$3.6M
Functional Analysis of Structure Specific Nucleases in Genome Stability and CancersR50CA211397 · NCI · BECKMAN RESEARCH INSTITUTE/CITY OF HOPE · PI ZHENG, LI · 2016 to 2025
$3.3M
NCI NIH HHS P30 CA033572NCI NIH HHS R01 CA085344NCI NIH HHS R01 CA195612NCI NIH HHS R50 CA211397
6 · The paper itself

Abstract

DNA2 is a nuclease/helicase that is involved in Okazaki fragment maturation, replication fork processing, and end resection of DNA double-strand breaks. Similar such helicase activity for resolving secondary structures and structure-specific nuclease activity are needed during DNA replication to process the chromosome-specific higher order repeat units present in the centromeres of human chromosomes. Here, we show that DNA2 binds preferentially to centromeric DNA The nuclease and helicase activities of DNA2 are both essential for resolution of DNA structural obstacles to facilitate DNA replication fork movement. Loss of DNA2-mediated clean-up mechanisms impairs centromeric DNA replication and CENP-A deposition, leading to activation of the ATR DNA damage checkpoints at centromeric DNA regions and late-S/G2 cell cycle arrest. Cells that escape arrest show impaired metaphase plate formation and abnormal chromosomal segregation. Furthermore, the DNA2 inhibitor C5 mimics DNA2 knockout and synergistically kills cancer cells when combined with an ATR inhibitor. These findings provide mechanistic insights into how DNA2 supports replication of centromeric DNA and give further insights into new therapeutic strategies.

Indexed as

DNA ReplicationGenomic InstabilityCell CycleCell LineCentromereChromosomes, HumanDNA HelicasesHumansDNA2 protein, humanDNA Helicasescell cycle arrestcentromerecentromeric DNA replicationchromosome segregationDNA2

Identifiers

PMID29773570
PMCPMC6043852
OpenAlexW2804290503

What OpenQuestion holds

Textmetadata
LicenceCC BY
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.