Continuous nuclear envelope surveillance is required for DNA double strand break repair

Area of Science:

• Cell Biology
• Molecular Biology
• Genetics

Background:

• Precise repair of DNA double-strand breaks (DSBs) is critical for maintaining genome stability.
• Homologous recombination (HR) is the preferred error-free repair pathway for DSBs, utilizing sister chromatids as templates.
• In Saccharomyces cerevisiae, this HR preference persists into late mitosis (late-M) even after sister chromatids have separated.

Purpose of the Study:

• To investigate the role of the nuclear envelope (NE) protein Msc1 in late-M DSB repair.
• To elucidate the function of Msc1 and its relationship with nuclear envelope integrity and DSB repair mechanisms.

Main Methods:

• Yeast genetics and microscopy techniques were employed.
• Analysis of Msc1 localization and function within the nuclear envelope.
• Investigation of nuclear morphology, nuclear pore complex (NPC) positioning, and DSB repair phenotypes.

Main Results:

• Msc1 localizes to the NE lumen.
• Msc1 depletion causes nucleus over-compartmentalization and NPC mislocation, independent of DSBs.
• These NE defects are partially shared with the ESCRT-III complex, known for NE healing.
• Abnormal NE phenotypes are observed throughout the cell cycle and in DSB-induced G2/M arrest.

Conclusions:

• Nuclear envelope (NE) homeostasis is essential for efficient double-strand break (DSB) repair.
• Msc1 plays a significant role in maintaining NE integrity, which is linked to DSB repair processes.
• Dysregulation of NE homeostasis can lead to nuclear abnormalities and potentially impact genome stability.