ANKLE1 processes chromatin bridges by cleaving mechanically stressed DNA.

Area of Science:

• Cell Biology
• Molecular Biology
• Genetics

Background:

• Chromatin bridges are subjected to significant tension during cell division.
• Breakage of these bridges by actomyosin forces can lead to severe genomic instability.
• Mechanisms for processing tension-bearing chromatin bridges are not fully understood.

Purpose of the Study:

• To investigate the role of ANKLE1 in processing chromatin bridges.
• To determine if ANKLE1 responds to DNA tension and supercoiling.
• To elucidate how cells maintain genome integrity during cell division.

Main Methods:

• Single-molecule analyses were employed.
• ANKLE1's activity on supercoiled and stretched DNA was assessed.
• DNA tension and supercoiling conditions were mimicked.

Main Results:

• ANKLE1 specifically cleaves supercoiled or mechanically stretched DNA.
• At high forces, ANKLE1 cuts both strands of negatively supercoiled DNA.
• This activity mirrors conditions where chromatin bridges expose DNA.

Conclusions:

• ANKLE1 functions as a DNA tension sensor.
• ANKLE1 resolves stretched chromatin bridges, preventing catastrophic rupture.
• Mechanical forces play a critical role in DNA bridge processing and genome stability.