Neither Mps1-T686D nor -T686E could restore spindle checkpoint function (Fig. S1B).
The T686A mutant, like the D664A mutant, was unable to restore either checkpoint signaling (Fig. 2B, 2C) or chromosome alignment (Fig. 2D).
In agreement with the inability of T686D or T686E to restore spindle checkpoint function, these mutants were also devoid of kinase activity (data not shown).
Similarly, artificially recruiting Mad1 in either bub1Δ or bub1-cm1 cells did not restore the checkpoint (Fig 2D and E).
(D ) Bub3R217A R239A is unable to restore a functional checkpoint when expressed in bub3Δ cells.
By ubiquitination of HDAC1, CHFR is able to reverse HDAC1-induced repression of p21 and thereby restore the p21-G1 checkpoint [ 28, 30, 31].
Specifically, expression of the N-terminal Sm-like domain of Sum2p, but not the full length Sum2p, was found to restore the G2/M checkpoint bypass in Cdc25p-overproducing cells, as well as in cells with mutations in Cdk2p and Wee1p, which show identical checkpoint defects [ 31].
Although mAbs targeting tumor associated antigens, such as anti-CD20 mAb and anti-Her2 mAb, directly recognize tumor cells and induce cell death, immune checkpoint inhibitors restore and augment the antitumor immune activities of cytotoxic T cells by blocking immune checkpoint molecules on T cells or their ligands on antigen presenting and tumor cells.
However, when broken forks are present, Swi3 functions to restore forks using a checkpoint-independent pathway, which is also important for proper establishment of sister chromatid cohesion.
