Shelterin reduces the accessibility of telomeric overhangs.
Nucleic Acids Res
; 50(22): 12885-12895, 2022 12 09.
Article
in En
| MEDLINE
| ID: mdl-36511858
ABSTRACT
Telomeres terminate with a 50-300 bases long single-stranded G-rich overhang, which can be misrecognized as a DNA damage repair site. Shelterin plays critical roles in maintaining and protecting telomere ends by regulating access of various physiological agents to telomeric DNA, but the underlying mechanism is not well understood. Here, we measure how shelterin affects the accessibility of long telomeric overhangs by monitoring transient binding events of a short complementary peptide nucleic acid (PNA) probe using FRET-PAINT in vitro. We observed that the POT1 subunit of shelterin reduces the accessibility of the PNA probe by â¼2.5-fold, indicating that POT1 effectively binds to and protects otherwise exposed telomeric sequences. In comparison, a four-component shelterin stabilizes POT1 binding to the overhang by tethering POT1 to the double-stranded telomeric DNA and reduces the accessibility of telomeric overhangs by â¼5-fold. This enhanced protection suggests shelterin restructures the junction between single and double-stranded telomere, which is otherwise the most accessible part of the telomeric overhang.
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Telomere
/
Shelterin Complex
Language:
En
Journal:
Nucleic Acids Res
Year:
2022
Type:
Article
Affiliation country:
United States