DNA Damage Response and Spindle Assembly Checkpoint Function throughout the Cell Cycle to Ensure Genomic Integrity


Checkpoints are surveillance pathways that monitor and correct cellular errors to ensure that the genome is transmitted intact through cell division; defects in checkpoints lead to human disease such as cancer. Two major checkpoint pathways that have been extensively studied are the DNA damage response and the spindle assembly checkpoint. As their names imply, they have been thought to monitor distinct chromosomal events during the cell cycle. Here, we used C. elegans proliferating germ cells and human cells to investigate the role of these checkpoints when either DNA is damaged or the spindle is perturbed. We discovered that these checkpoints function together in response to these different perturbations to ensure genome integrity. Our studies have important implications for cancer treatments, as many cancer chemotherapies target one of these checkpoint pathways without consideration for the effect on the other pathway.


Vyšlo v časopise: DNA Damage Response and Spindle Assembly Checkpoint Function throughout the Cell Cycle to Ensure Genomic Integrity. PLoS Genet 11(4): e32767. doi:10.1371/journal.pgen.1005150
Kategorie: Research Article
prolekare.web.journal.doi_sk: 10.1371/journal.pgen.1005150

Souhrn

Checkpoints are surveillance pathways that monitor and correct cellular errors to ensure that the genome is transmitted intact through cell division; defects in checkpoints lead to human disease such as cancer. Two major checkpoint pathways that have been extensively studied are the DNA damage response and the spindle assembly checkpoint. As their names imply, they have been thought to monitor distinct chromosomal events during the cell cycle. Here, we used C. elegans proliferating germ cells and human cells to investigate the role of these checkpoints when either DNA is damaged or the spindle is perturbed. We discovered that these checkpoints function together in response to these different perturbations to ensure genome integrity. Our studies have important implications for cancer treatments, as many cancer chemotherapies target one of these checkpoint pathways without consideration for the effect on the other pathway.


Zdroje

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