Nuclear actin and DNA replication stress regulate telomere maintenance by telomerase

Area of Science:

• Cell Biology
• Molecular Biology
• Genetics

Background:

• Telomere maintenance is crucial for cellular stability.
• Telomerase recruitment to telomeres is regulated by replication stress and ATR kinase.
• The precise mechanism of telomerase recruitment remains unclear.

Purpose of the Study:

• To elucidate the mechanism of telomerase recruitment to telomeres.
• To investigate the role of nuclear actin in telomere elongation.
• To identify key regulators involved in this process.

Main Methods:

• Utilized immortal human cell lines.
• Investigated the role of nuclear filamentous actin.
• Examined the involvement of ATR, mTOR, WASP, ARP2/3, and myosin.
• Analyzed telomere tethering and telomerase localization under replication stress.

Main Results:

• Nuclear filamentous actin is essential for stable telomerase-telomere interaction.
• Telomerase recruitment and telomere elongation are actin-dependent.
• ATR and mTOR kinases regulate this actin-mediated process.
• Replication stress induces telomere tethering on actin fibers, facilitating telomerase access to stalled replication forks.

Conclusions:

• Nuclear actin network acts as a platform for telomerase recruitment during telomeric replication stress.
• This mechanism is vital for telomere length maintenance in human cells expressing telomerase.
• The findings reveal a novel pathway involving nuclear actin in regulating telomere homeostasis.