# Phage-encoded TelN inhibits bacterial Mre11-Rad50 nuclease to protect hairpin telomeres

## TL;DR

This paper shows how a phage protein called TelN protects its DNA ends from bacterial repair enzymes, revealing a new mechanism for telomere protection.

## Contribution

The study identifies TelN as a key protector of hairpin telomeres by inhibiting Mre11-Rad50 nuclease activity in bacteria.

## Key findings

- TelN is essential and sufficient to protect phage hairpin telomeres from Mre11-Rad50 processing.
- Protection requires TelN's DNA binding and protein-protein interactions with the MR complex.
- TelN's protection mechanism is independent of its resolution activity and C-terminal domains.

## Abstract

Ends of linear chromosomes require protection from host repair machinery that otherwise will mistake them for damaged DNA. The E. coli bacteriophage N15 harbors a linear genome with covalently closed hairpin ends formed by the phage-encoded telomere resolvase TelN. The double-strand break repair complex Mre11-Rad50 (MR, SbcCD in E. coli) specifically targets DNA termini, yet how hairpin telomeres evade host nuclease degradation in bacteria remains unknown. Here, we demonstrate that TelN is essential and sufficient to protect N15 phage-derived hairpin telomeres from MR processing in E. coli. Using a combination of genetic and biochemical approaches, we show that this protective function requires both TelN sequence-specific DNA binding and species-specific protein-protein interactions. Notably, we found that protection is independent of TelN’s resolution activity and does not require the C-terminal domains of TelN. Our findings reveal a potentially broad mechanism of telomere protection, providing insights into a conserved regulation of MR activity at chromosome ends across the tree of life.

Chromosome ends require protection from the DNA repair machinery. This work demonstrates that TelN protein, the telomere resolvase of E. coli phage N15, protects hairpin telomeres from processing by the host Mre11-Rad50 nuclease through distinct molecular mechanisms.

TelN is essential and sufficient to protect N15 phage-derived hairpin telomeres from Mre11-Rad50 processing.Protective functions require both TelN sequence-specific DNA binding and species-specific protein-protein interactions with the E. coli MR complex.Hairpin telomere protection is independent of TelN's resolution activity and of the C-terminal domains of TelN, locating a core protection mechanism to conserved N-terminal domains.

TelN is essential and sufficient to protect N15 phage-derived hairpin telomeres from Mre11-Rad50 processing.

Protective functions require both TelN sequence-specific DNA binding and species-specific protein-protein interactions with the E. coli MR complex.

Hairpin telomere protection is independent of TelN's resolution activity and of the C-terminal domains of TelN, locating a core protection mechanism to conserved N-terminal domains.

Bacteriophages with linear genomes evade telomere processing by bacterial host MR complexes via a telomere-resolution-independent function of their telomere resolvase.