title: Middle region of FancM interacts with Mhf and Rmi1 in silkworms, a species lacking the Fanconi anaemia (FA) core complex.
abstract: The Fanconi anaemia (FA) pathway is responsible for interstrand crosslink (ICL) repair. Among the FA core complex components, FANCM is believed to act as a damage sensor for the ICL-blocked replication fork and also as a molecular platform for FA core complex assembly and interaction with Bloom's syndrome (BS) complex that is thought to play an important role in the processing of DNA structures such as stalled replication forks. In the present study, we found that in silkworms, Bombyx mori, a species lacking the major FA core complex components (FANCA, B, C, E, F, and G), FancM is required for FancD2 monoubiquitination and cell proliferation in the presence of mitomycin C (MMC). Silkworm FancM (BmFancM) was phosphorylated in the middle regions, and the modification was associated with its subcellular localization. In addition, BmFancM interacted with Mhf1, a histone-fold protein, and Rmi1, a subunit of the BS complex, in the different regions. The interaction region containing at least these two protein-binding domains played an essential role in FancM-dependent resistance to MMC. Our results suggest that BmFancM also acts as a platform for recruitment of both the FA protein and the BS protein, although the silkworm genome seems to lose FAAP24, a FancM-binding partner protein in mammals.
authors.affiliation: Laboratory of Silkworm Science, Graduate School of Bioresource and Bioenvironmental Sciences, Kyushu University, Fukuoka, Japan.
authors.forename: R
authors.initials: R
authors.lastname: Sugahara
authors.forename: H
authors.initials: H
authors.lastname: Mon
authors.forename: J M
authors.initials: JM
authors.lastname: Lee
authors.forename: T
authors.initials: T
authors.lastname: Kusakabe
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D012831:Bombyx / Q000235:genetics* / Q000378:metabolism; D002460:Cell Line; D049109:Cell Proliferation; D004260:DNA Repair; D004261:DNA Replication; D051856:Fanconi Anemia Complementation Group Proteins / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism; D019476:Insect Proteins / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism; D016685:Mitomycin / Q000494:pharmacology; D008969:Molecular Sequence Data; D010766:Phosphorylation; D020133:Reverse Transcriptase Polymerase Chain Reaction; D016415:Sequence Alignment; D054875:Ubiquitination
chemical_list: D051856:Fanconi Anemia Complementation Group Proteins; D019476:Insect Proteins; D016685:Mitomycin
keywords: Bloom's pathway; DNA repair; Fanconi anaemia pathway; insect