TRF2 promotes, remodels and protects telomeric Holliday junctions

TRF2 promotes, remodels and protects telomeric Holliday junctions.

The ability of the telomeric DNA-binding protein, TRF2, to stimulate t-loop formation while preventing t-loop deletion is believed to be crucial to maintain telomere integrity in mammals. However, little is known on the molecular mechanisms behind these properties of TRF2. In this report, we show that TRF2 greatly increases the rate of Holliday junction (HJ) formation and blocks the cleavage by...

Telomeric protein TRF2 protects Holliday junctions with telomeric arms from displacement by the Werner syndrome helicase

WRN protein loss causes Werner syndrome (WS), which is characterized by premature aging as well as genomic and telomeric instability. WRN prevents telomere loss, but the telomeric protein complex must regulate WRN activities to prevent aberrant telomere processing. Telomere-binding TRF2 protein inhibits telomere t-loop deletion by blocking Holliday junction (HJ) resolvase cleavage activity, but...

Notch remodels junctions

Targeting Holliday Junctions

Holliday junctions are formed as an intermediate during DNA recombination as the two strands come together. Recombination occurs during meiosis, and also during DNA double strand repair. Trapping this branched intermediate could prevent DNA repair from occurring in cells which would prove beneficial during cancer treatment. There are many enzymes that cleave Holliday junctions. One such enzyme,...

The Bloom syndrome helicase BLM interacts with TRF2 in ALT cells and promotes telomeric DNA synthesis.

Telomerase-negative immortalized human cells maintain telomeres by alternative lengthening of telomeres (ALT) pathway(s), which may involve homologous recombination. We find that endogenous BLM protein co-localizes with telomeric foci in ALT human cells but not telomerase positive immortal cell lines or primary cells. BLM interacts in vivo with the telomeric protein TRF2 in ALT cells, as detect...