Sunday, September 28, 2025
Science
No Result
View All Result
  • Login
  • HOME
  • SCIENCE NEWS
  • CONTACT US
  • HOME
  • SCIENCE NEWS
  • CONTACT US
No Result
View All Result
Scienmag
No Result
View All Result
Home Science News Cancer

Unraveling the role of CDCA7 in maintenance of DNA methylation

August 26, 2024
in Cancer
Reading Time: 3 mins read
0
CDCA7 specifically binds to hemi-methylated DNA in the nucleosome
66
SHARES
596
VIEWS
Share on FacebookShare on Twitter
ADVERTISEMENT

DNA methylation, a process by which methyl groups are added to DNA molecules, is essential for the maintenance of DNA and the overall health of an organism. Disruptions in the standard DNA methylation patterns can lead to immunodeficiency and diseases such as cancer. Helicase lymphoid-specific (HELLS) is an enzyme that facilitates DNA methylation by remodeling the nucleosome – the tightly packed structure of DNA wound around histone proteins. The absence of HELLS or its activator, cell division cycle associated 7 (CDCA7) is known to be a factor that leads to the disruption of DNA methylation. Mutations in the genes that code for HELLS and CDCA7 cause rare disorder immunodeficiency, centromeric instability, and facial anomalies (ICF) syndrome.

CDCA7 specifically binds to hemi-methylated DNA in the nucleosome

Credit: Kyohei Arita, Yokohama City University

DNA methylation, a process by which methyl groups are added to DNA molecules, is essential for the maintenance of DNA and the overall health of an organism. Disruptions in the standard DNA methylation patterns can lead to immunodeficiency and diseases such as cancer. Helicase lymphoid-specific (HELLS) is an enzyme that facilitates DNA methylation by remodeling the nucleosome – the tightly packed structure of DNA wound around histone proteins. The absence of HELLS or its activator, cell division cycle associated 7 (CDCA7) is known to be a factor that leads to the disruption of DNA methylation. Mutations in the genes that code for HELLS and CDCA7 cause rare disorder immunodeficiency, centromeric instability, and facial anomalies (ICF) syndrome.

Understanding why CDCA7-HELLS is crucial for maintaining DNA methylation is vital for gaining insights into the mechanism of disorders such as ICF syndrome. In a recent study published in Science Advances on August 23 2024, researchers have found that CDCA7 can recognize hemimethylation of DNA—a state where one strand of the DNA’s double helix is methylated but not the other—and recruit HELLS to complete methylation of the DNA. The researchers found that the hemimethylation-sensing zinc finger (HMZF) of CDCA7, which has been conserved throughout evolution, is key to its ability to perform maintenance DNA methylation. “We found that the CDCA7 gene, known as the causative gene of ICF syndrome, promotes DNA methylation by controlling the ubiquitination of histone H3 through specific binding to hemimethylated DNA on nucleosomes,” explains Associate Professor Atsuya Nishiyama from the Division of Cancer Cell Biology, The Institute of Medical Science, The University of Tokyo, one of the lead researchers of the study.

Dr. Nishiyama, together with Professor Hironori Funabiki and Dr. Isabel Wassing at The Rockefeller University, Professor Kyohei Arita from Yokohama City University and Professor Makoto Nakanishi from The University of Tokyo, examined the structure of the complex formed by CDCA7 and the nucleosome using single particle cryo-electron microscopy. They found that CDCA7, unlike other DNA methylation activators, uniquely identifies hemimethylated DNA in the outward-facing major groove of the nucleosome core particle (NCP). This discovery explains why mutations in CDCA7 associated with ICF syndrome led to a defective DNA maintenance methylation mechanism.

“Our findings suggest that CDCA7 and HELLS promote DNA methylation in a mechanism distinct from de novo DNA methylation, which is now consolidated by our demonstration that the CDCA7 HMZF domain specifically recognizes hemimethylated CpG, the substrate of the maintenance DNA methyltransferase DNMT1. ICF disease-associated mutations in the CDCA7 gene abolish its hemimethylated DNA binding, supporting the functional importance of hemimethylation detection by the CDCA7 gene,” Dr. Nishiyama notes.

These pioneering findings not only advance potential therapies for ICF syndrome but also open new frontiers in cancer prevention and anti-aging. Disruptions in DNA methylation is linked to cancer, while inefficient methylation is a hallmark of cellular aging. “Our study lays the groundwork for the development of new DNA methylation inhibitors and therapeutic drugs for ICF syndrome. Therapies that artificially regulate CDCA7-dependent DNA methylation may also prevent cancer and aging and help extend healthy lifespan,” Dr. Nishiyama concludes.



Journal

Science Advances

DOI

10.1126/sciadv.adp5753

Method of Research

Experimental study

Subject of Research

Cells

Article Title

CDCA7 is an evolutionarily conserved hemimethylated DNA sensor in eukaryotes

Article Publication Date

23-Aug-2024

Share26Tweet17
Previous Post

Old chemo drug, new pancreatic cancer therapy?

Next Post

Early galaxies were not too big for their britches after all

Related Posts

blank
Cancer

CSNK1E Influences Hepatocellular Carcinoma Growth and Migration

September 27, 2025
blank
Cancer

Evaluating Predictive Models for Leukemia Types: Review

September 27, 2025
blank
Cancer

Navigating CDK4/6 Inhibitor Hepatotoxicity in Breast Cancer

September 27, 2025
blank
Cancer

Evaluating Liver Stiffness in Children with Biliary Atresia

September 27, 2025
blank
Cancer

Vitamin D’s Role in Leukemia: Mechanisms and Therapy

September 27, 2025
blank
Cancer

Researchers from the University of Cincinnati Cancer Center Showcase Radiation Oncology Advances at National Conference

September 26, 2025
Next Post
Small portion of CEERS survey

Early galaxies were not too big for their britches after all

  • Mothers who receive childcare support from maternal grandparents show more parental warmth, finds NTU Singapore study

    Mothers who receive childcare support from maternal grandparents show more parental warmth, finds NTU Singapore study

    27560 shares
    Share 11021 Tweet 6888
  • University of Seville Breaks 120-Year-Old Mystery, Revises a Key Einstein Concept

    969 shares
    Share 388 Tweet 242
  • Bee body mass, pathogens and local climate influence heat tolerance

    646 shares
    Share 258 Tweet 162
  • Researchers record first-ever images and data of a shark experiencing a boat strike

    512 shares
    Share 205 Tweet 128
  • Groundbreaking Clinical Trial Reveals Lubiprostone Enhances Kidney Function

    470 shares
    Share 188 Tweet 118
Science

Embark on a thrilling journey of discovery with Scienmag.com—your ultimate source for cutting-edge breakthroughs. Immerse yourself in a world where curiosity knows no limits and tomorrow’s possibilities become today’s reality!

RECENT NEWS

  • Encoding Levels Impact Fearful, Disgusting Memory Recall
  • Nickel-Doped α-Bi2O3 Boosts Biomass Carbon Supercapacitors
  • Genome Study Reveals Pediococcus Genes Tied to Beer Spoilage
  • Social Cognition and Connectedness in Syrian Refugees

Categories

  • Agriculture
  • Anthropology
  • Archaeology
  • Athmospheric
  • Biology
  • Blog
  • Bussines
  • Cancer
  • Chemistry
  • Climate
  • Earth Science
  • Marine
  • Mathematics
  • Medicine
  • Pediatry
  • Policy
  • Psychology & Psychiatry
  • Science Education
  • Social Science
  • Space
  • Technology and Engineering

Subscribe to Blog via Email

Enter your email address to subscribe to this blog and receive notifications of new posts by email.

Join 5,184 other subscribers

© 2025 Scienmag - Science Magazine

Welcome Back!

Login to your account below

Forgotten Password?

Retrieve your password

Please enter your username or email address to reset your password.

Log In
No Result
View All Result
  • HOME
  • SCIENCE NEWS
  • CONTACT US

© 2025 Scienmag - Science Magazine

Discover more from Science

Subscribe now to keep reading and get access to the full archive.

Continue reading