title: Human KIAA1018/FAN1 nuclease is a new mitotic substrate of APC/C(Cdh1).
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.
authors.affiliation: State Key Laboratory of Oncology in South China, Department of Experimental Research, Sun Yat-sen University Cancer Center, Guangzhou, Guangdong 510060, PR China.
authors.forename: Fenju
authors.initials: F
authors.lastname: Lai
authors.forename: Kaishun
authors.initials: K
authors.lastname: Hu
authors.forename: Yuanzhong
authors.initials: Y
authors.lastname: Wu
authors.forename: Jianjun
authors.initials: J
authors.lastname: Tang
authors.forename: Yi
authors.initials: Y
authors.lastname: Sang
authors.forename: Jingying
authors.initials: J
authors.lastname: Cao
authors.forename: Tiebang
authors.initials: T
authors.lastname: Kang
mesh_terms: D064173:Anaphase-Promoting Complex-Cyclosome; D015703:Antigens, CD; D001859:Bone Neoplasms / Q000378:metabolism / Q000473:pathology; D015820:Cadherins / Q000235:genetics / Q000378:metabolism*; D064199:Cdc20 Proteins; D018797:Cell Cycle Proteins / Q000235:genetics / Q000378:metabolism; D045744:Cell Line, Tumor; D004706:Endodeoxyribonucleases; D005090:Exodeoxyribonucleases / Q000235:genetics / Q000378:metabolism*; D057809:HEK293 Cells; D006801:Humans; D008938:Mitosis; D064251:Multifunctional Enzymes; D012516:Osteosarcoma / Q000378:metabolism / Q000473:pathology; D043743:Ubiquitin-Protein Ligase Complexes / Q000235:genetics / Q000378:metabolism*
chemical_list: D015703:Antigens, CD; C513384:CDH1 protein, human; D015820:Cadherins; D064199:Cdc20 Proteins; D018797:Cell Cycle Proteins; D064251:Multifunctional Enzymes; C577488:CDC20 protein, human; D043743:Ubiquitin-Protein Ligase Complexes; D064173:Anaphase-Promoting Complex-Cyclosome; D004706:Endodeoxyribonucleases; D005090:Exodeoxyribonucleases; C551063:FAN1 protein, human