Additional complexes, which, similar to cohesin, contain the SMC1 SMC3 heterodimer, were suggested to be involved in DNA repair and/or in intra-S checkpoint function, such as the BRCA1 supercomplex (BASC) (Yazdi et al, 2002) and the recombination complex RC-1(Jessberger et al, 1996).
In summary, although ESCs lack the typical p53-dependent functions, such as cell cycle G1/S checkpoint and senescence, p53 maintains the genomic stability of ESCs by coordinating their DNA damage responses and self-renewal capability.
Aurora B, a chromosomal segregation protein, is expressed during mitosis and carries out vital functions such as chromosome alignment, a spindle-checkpoint function, and cytokinesis [ 40].
In addition, the lead compounds 1 and 13 inhibit Mps1 kinase enzymatic activity with IC50 values from 0.356 μM to 0.809 μM, and inhibited Mps1-associated cellular functions such as centrosome duplication and the spindle checkpoint in triple negative breast cancer cells.
Co-inhibitory and co-stimulatory immune checkpoint receptors are required for full T-cell activation and effector functions such as the production of cytokines.
Tumor suppressor genes can be classified by their various functions, such as those which operate as transcription factors, DNA damage sensors, cell cycle checkpoint controllers, etc. [5].
The apparent checkpoint proficiency of BubR1Δ432 484 may indicate that BubR1 localization to kinetochores is not essential for checkpoint function, as it implies that substantial amounts of MCC can be generated even when BubR1/Bub3 cannot be recruited to kinetochores.
Other studies have shown that cells with partial loss of the checkpoint function are resistant to microtubule destabilizing drugs such as nocodazole but not to microtubule stabilizing drugs such as Taxol.
Immune checkpoint proteins, such as PD-1 and CTLA-4, can prevent the activation of T cells in immune system.
Clinical studies have also investigated the efficacy of combination therapies using anti-PD-1/PD-L1 togethers together with other checkpoint inhibitors, such as the anti-CTLA4 treatment ipilimumab.
These therapies have different mechanisms of action and include oncolytic viruses, checkpoint inhibitors, such as CTLA-4 or PD1/PD-L1 monoclonantibodiesies, and CSF-1R antibodies.
