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#cell cycle checkpoint

2 public questions tagged with this topic.

Cell Cycle Regulation

What is the role of the Spindle Assembly Checkpoint (SAC)?

Chromosome missegregation produces aneuploidy implicated in tumorigenesis, congenital disorders, and embryonic lethality, necessitating surveillance by spindle assembly checkpoint. Sensor is kinetochore assembled on CENP-A containing centromeric nucleosomes that binds microtubule plus ends via Ndc80 complex. Unattached kinetochores act as catalytic platforms where Mad1-Mad2 heterotetramer converts soluble open Mad2 into closed conformation that binds Cdc20. Together with BubR1, Bub3, and Bub1 phosphorylated by Mps1 kinase, they generate diffusible mitotic checkpoint complex that inhibits APC/C

Ref: Musacchio, Current Biology 2015, SAC Mechanism. Alberts 7th ed., Chapter 17, Mitosis Quality.

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Cell Cycle Regulation

The key regulatory checkpoint for DNA replication completion before mitosis is:

Before mitosis, cells must verify complete and accurate genome duplication to avoid mitotic breakage of under-replicated chromosomes. G2/M checkpoint operates as surveillance system mediated by ATR-Chk1 and ATM-Chk2 kinases activated by RPA-coated single-stranded DNA at stalled forks and double-strand breaks respectively. Chief effectors are Cdc25 phosphatase family isoforms B and C that normally remove inhibitory Thr14 and Tyr15 phosphorylations placed on CDK1 by Wee1 and Myt1 nuclear kinases, triggering abrupt CDK1 activation. Checkpoint kinases phosphorylate Cdc25B/C at Ser216 and Ser323 ge

Ref: Lodish et al., Molecular Cell Biology, 9th ed., Chapter 20: G2/M Checkpoint and Replication Completion.

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