MRX is a heterotrimeric complex composed of Mre11p, Rad50p, and Xrs2p that serves important roles in both DSB recognition, telomere capping, and checkpoint activation (Boulton and Jackson 1998; Nugent et al. 1998; Ritchie and Petes 2000; D'Amours and Jackson 2001; Grenon et al. 2001).
It seems that it is the role of Mrc1 at the replication fork that contributes to the vitality of telomere capping mutants, rather than its role in checkpoint activation.
This proposed "capping" function prevents cells from inducing a senescence checkpoint by protecting telomeres from recognition as damaged DNA even when they remain short [ 18, 22].
In the absence of the telomere capping protein Cdc13, budding yeast telomeres erode, resulting in checkpoint arrest.
This difference most likely reflects the fact that cdc13-1 mrc1Δ exo1Δ mutants have more severe telomere capping defect than cdc13-1 exo1Δ mutands and therefore activate a stronger checkpoint signal.
More recently, the capping function has expanded to include the concept of protecting telomeres from checkpoints as loss of a single telomere elicits a Rad9p-dependent cell cycle arrest (Sandell and Zakian 1993).
Careful analyses of growth properties of human fibroblasts and HMECs have shown that continued proliferation after checkpoint inactivation (via T antigen expression and p16INK4A loss, respectively) results in eventual loss of telomere capping function and impaired chromosomal stability.
Paradoxically, many checkpoint and DNA repair proteins associate with telomeres and contribute in important ways to telomeric functions, including capping.
Without the capping proteins, chromosome ends appear as double-stranded breaks to the cell's DNA damage detection mechanism, triggering a checkpoint response and ultimately cell cycle arrest (Longhese, 2008; Sandell and Zakian, 1993).
To cap it off, at a rebel checkpoint, one gunman, who they believed was from Saudi Arabia or Yemen, ordered Ola, who wears a loosely draped head scarf, to cover her face.
Our results showed that the expression of p-Chk1 and p-Chk2 was increased in CaP-RR (PC-3RR, DU145RR and LNCaPRR) cells compared with that in CaP-control cells, whereas no change was found in t-Chk1 and t-Chk2 expression between CaP-RR and CaP-control cells, which indicated that checkpoint proteins (p-Chk1 and p-Chk2) are activated in CaP-RR cells and associated with CaP radioresistance.
