Interaction of FLASH with arsenite resistance protein 2 is involved in cell cycle progression at S phase.
FLASH has been shown to be required for S phase progression and to interact with a nuclear protein, ataxia-telangiectasia locus (NPAT), a component of Cajal bodies in the nucleus and an activator of histone transcription. We investigated the role of human FLASH by using an inducible FLASH knockdown system in the presence or absence of various mutant forms of mouse FLASH. While carboxyl-terminal deletion mutants of FLASH, which do not interact with NPAT, can support S phase progression, its amino-terminal deletion mutants, which are unable to self associate, cannot support S phase progression, replication-dependent histone transcription, or the formation of Cajal bodies. Furthermore, FLASH was shown to be associated with arsenite resistance protein 2 (ARS2) through its central region, which is composed of only 13 amino acids. The expression of ARS2 and the interaction between FLASH and ARS2 are required for S phase progression. Taking these results together, FLASH functions in S phase progression through interaction with ARS2.
Kiriyama
Maria
M
Laboratory of Molecular and Cellular Biology, Graduate School of Biostudies, Kyoto University, Sakyo-ku, Kyoto, Japan.
Kobayashi
Yohei
Y
Saito
Motoki
M
Ishikawa
Fuyuki
F
Yonehara
Shin
S
D000595:Amino Acid Sequence; D000818:Animals; D002135:Calcium-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D002453:Cell Cycle / Q000502:physiology*; D018797:Cell Cycle Proteins / Q000235:genetics / Q000378:metabolism*; D002460:Cell Line; D006657:Histones / Q000235:genetics / Q000378:metabolism; D006801:Humans; D051379:Mice; D008969:Molecular Sequence Data; D009687:Nuclear Proteins / Q000235:genetics / Q000378:metabolism*; D012313:RNA / Q000235:genetics / Q000378:metabolism; D011993:Recombinant Fusion Proteins / Q000235:genetics / Q000378:metabolism; D016196:S Phase / Q000502:physiology*; D016415:Sequence Alignment; D014158:Transcription, Genetic
D002135:Calcium-Binding Proteins; C119301:Casp8ap2 protein, mouse; D018797:Cell Cycle Proteins; D006657:Histones; D009687:Nuclear Proteins; D011993:Recombinant Fusion Proteins; C527299:SRRT protein, human; C543824:p220(NPAT) protein, mouse; C068921:p80-coilin; D012313:RNA