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

Chinese journal of cancer (2012-08-03)
Fenju Lai, Kaishun Hu, Yuanzhong Wu, Jianjun Tang, Yi Sang, Jingying Cao, Tiebang Kang
ABSTRACT

A recently identified protein, FAN1 (FANCD2-associated nuclease 1, previously known as KIAA1018), is a novel nuclease associated with monoubiquitinated FANCD2 that is required for cellular resistance against DNA interstrand crosslinking (ICL) agents. The mechanisms of FAN1 regulation have not yet been explored. Here, we provide evidence that FAN1 is degraded during mitotic exit, suggesting that FAN1 may be a mitotic substrate of the anaphase-promoting cyclosome complex (APC/C). Indeed, Cdh1, but not Cdc20, was capable of regulating the protein level of FAN1 through the KEN box and the D-box. Moreover, the up- and down-regulation of FAN1 affected the progression to mitotic exit. Collectively, these data suggest that FAN1 may be a new mitotic substrate of APC/CCdh1 that plays a key role during mitotic exit.

MATERIALS
Product Number
Brand
Product Description

Millipore
ANTI-FLAG® antibody produced in rabbit, affinity isolated antibody, buffered aqueous solution
Millipore
ANTI-FLAG® M1 Agarose Affinity Gel
Sigma-Aldrich
Anti-phospho-Histone H3 (Ser10) Antibody, Mitosis Marker, Upstate®, from rabbit