TZAP mediated BTR localization to telomeres

Authors

• AA Thaivalappil
• WA Cabral
• UL Tavarez
• MR Erdos
• FS Collins

Abstract

Maintenance of telomere length is a critical process required to ensure genome stability. This process involves the balancing between process that result in telomere shortening and telomere lengthening. Excessive shortening results in replicative senescence whereas unregulated lengthening allows for unlimited cell proliferation and increase risk of cancer development. A critical factor involved in telomere length homeostasis is TZAP (telomeric zinc finger–associated protein). This protein binds specifically to telomeric repeat but shows preferential binding to long telomeres. Upon binding TZAP triggers rapid telomere deletion characterized by generation of extra-chromosomal telomeric DNA (ECTR) circles. The TZAP-mediated generation of ECTR is dependent on a protein complex called Bloom (BLM)-Topoisomerase lll α-RMI1-RMI2 (BTR). However, the specific nature of the relationship between TZAP and BTR is not fully understood. Here we show that BLM is recruited to telomeres directly by TZAP through its two putative SIM domains, since alterations in these domains significantly decreases the localization. Additionally, we demonstrate that TZAP can recruit BLM to telomeres independently of PML (promyelocytic leukemia protein), a known recruiter of BLM. These results contribute to our understanding of the complex relationship between TZAP and BTR in telomere biology.

Scientific Focus Area: Chromosome Biology

This page was last updated on Monday, September 25, 2023