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 interstra...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/C Cdh1 that plays a key role during mitotic exit.展开更多
基金supported by grants from Natural Science Foundation of Guangdong Province(No.10251008901000000 toT.K.)Ph.D.Program Foundation of Ministry of Education of China(No.20100171110079toT.K.)China Post doctoral Science Foundation(No.20110490966)
文摘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/C Cdh1 that plays a key role during mitotic exit.
