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The role of the APC/C-Cdh1 in the response to DNA damage

Roorda, M.M. (2015) The role of the APC/C-Cdh1 in the response to DNA damage. Bachelor's Thesis, Biology.

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The anaphase-promoting complex (APC/C) is an ubiquitin ligase that has a crucial function in the regulation of the cell cycle. The APC/C is active during mitosis and G1 of the cell cycle and ubiquitylates proteins to mark them for degradation, but only when activating proteins Cdc20 or Cdh1 interact with the APC/C. Targets of the APC/C are regulators of the cell cycle, such as Cyclins, Securin and kinases (Aurora A, Plk1). Degradation of these proteins controls processes such as entry of mitosis, the metaphase to anaphase transition and exit from mitosis and is thereby responsible for initiating the transition to the next phase of the cell cycle. Appropriate regulation of the APC/C contributes to the correct sequence of events through the cell cycle. In response to DNA damage, DNA repair mechanisms will cooperate with cell cycle regulators to halt the cell cycle. This will create more time for reparation of DNA and prevent the cell from initiating premature transition to the next phase while damaged. Cellular responses to DNA damage are regulated by two kinase signalling cascades, the ATR-Chk1 and ATM-Chk2 pathways. This induces a fast-acting but transient response, mediated by kinases, and a slow-acting response that is mediated by a transcription-dependent (p53/p21) pathway. Both pathways result in the inhibition of Cyclin-Cdk complexes and thereby induce cell cycle arrest. In response to DNA damage in G2, transition to mitosis must be prevented. Remarkably, APC/CCdh1 is activated in this process, although the APC/C only gets activated during mitosis and G2 of the unperturbed cell cycle. Cdc14b activity and p21-dependent inhibition of Emi1 induce this APC/CCdh1 activity. The activation of APC/CCdh1 may have interesting functions in the DNA damage response, such as maintaining a stable G2 arrest, permanent cell cycle exit, promoting DNA repair or induce mitotic catastrophe.

Item Type: Thesis (Bachelor's Thesis)
Degree programme: Biology
Thesis type: Bachelor's Thesis
Language: English
Date Deposited: 15 Feb 2018 08:04
Last Modified: 15 Feb 2018 08:04

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