Microscopic view of telomere repair by NEIL3 enzyme.

Can This 'Fountain of Youth' Enzyme Protect Your DNA?

Elliot Brynn in Health & Wellness November 2025 • 4 min read.

"New research highlights the vital role of NEIL3 in repairing telomere damage and securing chromosome segregation, potentially extending cellular lifespan."

In the quest for understanding aging and cellular health, scientists are constantly exploring the intricate mechanisms that keep our cells functioning correctly. Among these mechanisms, DNA repair processes stand out as crucial for maintaining genomic stability and preventing the onset of age-related diseases. Telomeres, the protective caps at the end of our chromosomes, are particularly vulnerable to damage, and their health is critical for overall cellular well-being.

Recent research has shed light on the role of a specific enzyme, NEIL3, in repairing damage to telomeres. This enzyme appears to be a key player in ensuring that chromosomes segregate correctly during cell division, a process essential for preventing genomic instability. Understanding how NEIL3 functions could provide new insights into how we can protect our DNA and potentially extend our healthspan.

This article delves into the groundbreaking findings about NEIL3, exploring its functions, its interactions with other proteins, and its potential implications for cellular health and longevity. By understanding the science behind NEIL3, we can appreciate the importance of DNA repair and the possibilities it holds for future health interventions.

What is NEIL3 and Why Is It Important for Telomere Repair?

Microscopic view of telomere repair by NEIL3 enzyme.

NEIL3, a member of the Nei-like DNA glycosylase family, is an enzyme that plays a crucial role in DNA repair. Unlike other members of its family, NEIL3 has a unique structure featuring an exceptionally long, intrinsically disordered C-terminal domain (CTD). This CTD sets NEIL3 apart and is believed to be key to its specific functions within the cell. Recent studies have highlighted NEIL3's critical role in repairing oxidative damage to telomeres, the protective caps at the ends of our chromosomes.

Telomeres are particularly vulnerable to oxidative damage because of their guanine-rich sequences, which are highly susceptible to reactive oxygen species (ROS). If this damage is not repaired, it can lead to telomere dysfunction, causing a range of cellular problems, including genomic instability and mitotic defects. NEIL3's activity ensures that these telomeres are protected, maintaining the integrity of our DNA during cell division.

Mitotic Defects: Loss of NEIL3 results in errors during cell division.
Telomere Dysfunction: NEIL3 prevents telomeres from malfunctioning.
TRF1 Interaction: NEIL3 interacts with TRF1 to localize to telomeres.
Repair Complex: NEIL3 works with PCNA and FEN1 in a DNA repair complex.

The importance of NEIL3 is underscored by its activity in highly proliferative cells, including cancer cells. These rapidly dividing cells are under constant stress and require robust DNA repair mechanisms to maintain their genomic integrity. NEIL3’s specific activity at telomeres during the S/G2 phases of the cell cycle ensures that any damage is promptly addressed, preventing the accumulation of mutations and chromosomal abnormalities.

Why This Matters

The discovery of NEIL3's role in telomere repair offers a promising avenue for future research into age-related diseases and cancer. By understanding how this enzyme works and how it interacts with other proteins, scientists may be able to develop new therapies to enhance DNA repair, protect telomeres, and promote genomic stability. This could potentially lead to interventions that extend cellular lifespan, reduce the risk of cancer, and improve overall health.

About this Article -

This article was crafted using a human-AI hybrid and collaborative approach. AI assisted our team with initial drafting, research insights, identifying key questions, and image generation. Our human editors guided topic selection, defined the angle, structured the content, ensured factual accuracy and relevance, refined the tone, and conducted thorough editing to deliver helpful, high-quality information.See our About page for more information.

This article is based on research published under:

DOI-LINK: 10.1016/j.celrep.2017.08.020, Alternate LINK

Title: Neil3 Repairs Telomere Damage During S Phase To Secure Chromosome Segregation At Mitosis

Subject: General Biochemistry, Genetics and Molecular Biology

Journal: Cell Reports

Publisher: Elsevier BV

Authors: Jia Zhou, Jany Chan, Marie Lambelé, Timur Yusufzai, Jason Stumpff, Patricia L. Opresko, Markus Thali, Susan S. Wallace

Published: 2017-08-01

Everything You Need To Know

What is NEIL3, and what specific role does it play in telomere maintenance and repair?

NEIL3 is a member of the Nei-like DNA glycosylase family and an enzyme crucial for DNA repair, especially at telomeres. Unlike other members of its family, NEIL3 features a long C-terminal domain (CTD). Its main function is to repair oxidative damage in telomeres, which are prone to damage due to their guanine-rich sequences. Without NEIL3, telomere dysfunction can occur, leading to genomic instability and mitotic defects.

How does NEIL3 interact with other proteins like TRF1, PCNA, and FEN1 to facilitate DNA repair at the telomeres?

NEIL3 interacts with TRF1 to properly position itself at the telomeres, where it can perform its DNA repair duties. It also collaborates with PCNA and FEN1 as part of a larger DNA repair complex. These interactions are critical for ensuring that telomere damage is efficiently and accurately repaired, preventing genomic instability.

What are telomeres, and why is it crucial for NEIL3 to protect them from oxidative damage?

Telomeres are the protective caps at the ends of our chromosomes. They are susceptible to damage, especially oxidative damage, due to their guanine-rich sequences. When telomeres are damaged and not repaired, it can lead to telomere dysfunction, genomic instability, and mitotic defects. Maintaining telomere integrity is essential for overall cellular health and preventing age-related diseases and cellular dysfunction.

What are the potential implications of NEIL3's role in DNA repair for age-related diseases and cancer research?

Recent research indicates that NEIL3 is highly active in rapidly dividing cells, such as cancer cells, to maintain genomic integrity. By understanding NEIL3's function and interactions, scientists may develop therapies to enhance DNA repair, protect telomeres, and promote genomic stability. This could lead to interventions extending cellular lifespan, reducing cancer risk, and improving overall health, opening a path for creating drugs to prevent damage.

The structure of NEIL3 has an exceptional long, intrinsically disordered C-terminal domain (CTD). What are the significance and function of NEIL3's C-terminal domain (CTD), and what future studies could improve the understanding of NEIL3?

NEIL3's unique long, intrinsically disordered C-terminal domain (CTD) is believed to be key to its specific functions within the cell. While the research highlights the importance of the CTD in NEIL3's activity, the exact mechanisms by which the CTD influences NEIL3's function are not completely understood. Future studies could focus on elucidating these mechanisms to fully understand NEIL3's role in DNA repair and its potential as a therapeutic target.