ZBTB10 binds the telomeric variant repeat TTGGGG and interacts with TRF2

Area of Science:

• Molecular Biology
• Genetics
• Cell Biology

Background:

• Telomeres protect chromosome ends and are crucial for genome stability.
• Alternative Lengthening of Telomeres (ALT) mechanism involves variant repeat sequences.
• Previous studies identified transcription factors binding to TCAGGG repeats in ALT cells.

Purpose of the Study:

• To identify proteins that bind to other variant telomere repeat sequences.
• To characterize the binding of ZBTB10 to TTGGGG repeats.

Main Methods:

• Protein-DNA binding assays to demonstrate ZBTB10 interaction with TTGGGG repeats.
• Co-localization studies in ALT-positive U2OS cells.
• Interaction studies with TRF2/RAP1 complex.

Main Results:

• ZBTB10 is identified as the first protein to bind TTGGGG variant repeats.
• Direct binding of ZBTB10 to TTGGGG repeats with nanomolar affinity was confirmed.
• ZBTB10 co-localizes with a subset of telomeres in ALT cells and interacts with TRF2/RAP1.

Conclusions:

• ZBTB10 is a novel variant repeat binding protein at ALT telomeres.
• This discovery contributes to understanding telomere maintenance in ALT cells.
• ZBTB10 plays a role in ALT telomere structure and function.