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Human KIAA1018/FAN1 nuclease is a new mitotic substrate of APC/C(Cdh1)

Fenju Lai1, Kaishun Hu, Yuanzhong Wu

  • 1State Key Laboratory of Oncology in South China, Department of Experimental Research, Sun Yat-sen University Cancer Center, Guangzhou, Guangdong 510060, PR China.

Chinese Journal of Cancer
|August 3, 2012
PubMed

Insights

FAN1 (FANCD2-associated nuclease 1) is degraded during mitotic exit, indicating it is a substrate of the APC/CCdh1 complex. This regulation is crucial for proper progression through mitotic exit.

Area of Science:

  • Cell Biology
  • Molecular Biology
  • Genetics

Background:

  • FAN1 (FANCD2-associated nuclease 1) is a novel nuclease essential for DNA interstrand crosslinking (ICL) resistance.
  • Mechanisms regulating FAN1 levels remain largely unexplored.

Purpose of the Study:

  • To investigate the regulatory mechanisms controlling FAN1 protein levels.
  • To determine if FAN1 is a substrate of the anaphase-promoting complex (APC/C).

Main Methods:

  • Investigated FAN1 degradation during mitotic exit.
  • Assessed the role of APC/C subunits (Cdh1 and Cdc20) in FAN1 regulation.
  • Utilized KEN box and D-box motifs for regulatory analysis.
  • Examined the impact of FAN1 up- and down-regulation on mitotic exit progression.

Main Results:

  • FAN1 protein levels decrease during mitotic exit.
  • Cdh1, but not Cdc20, regulates FAN1 protein levels via its KEN box and D-box.
  • Altering FAN1 levels impacts the progression of mitotic exit.

Conclusions:

  • FAN1 is a novel mitotic substrate of the APC/CCdh1 complex.
  • FAN1 plays a critical role in the process of mitotic exit.

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