A role for PCNA modification in telomere elongation

As the DNA is being replicated, the ends of each chromosome shorten (the “end replication problem”). For this reason, chromosomes are capped by special structures called telomeres which can be elongated by the activity of telomerase. Rif1 and Rif2 are two negative regulators of telomerase, and in their absence the telomeres are hyper elongated.

PCNA is a homo-trimeric ring that slides on the chromatin and serves as a docking site for replication and transcription related proteins. It is loaded onto the chromatin by a complex called RFC. PCNA can undergo SUMOylation on two conserved residues, K164 and K127, or ubiquitination at lysine 164. These modifications have already been implicated in genome stability processes.

Here we sought to investigate the connection to PCNA and its modifications, and in particularly SUMOylation, and telomere elongation. We report that elongation of telomeres resulting from mutations in TLM genes (Telomere Length Maintenance) can be suppressed by the additional mutation of the two lysines on PCNA. Since mutating only K164 does not have a similar effect, we conclude that SUMOylation is the important modification.

Notably, PCNA SUMOylation is not necessary for solving the “end replication problem”, and pol30KK127,164RR mutants have normal sized telomeres. Thus, the modification is required for sustained telomerase activity. We are currently investigating possible mechanisms by which PCNA SUMOylation promotes telomere hyper-elongation.