Requirement of SLD5 for early embryogenesis.
SLD5 forms a GINS complex with PSF1, PSF2 and PSF3, which is essential for the initiation of DNA replication in lower eukaryotes. Although these components are conserved in mammals, their biological function is unclear. We show here that targeted disruption of SLD5 in mice causes a defect in cell proliferation in the inner cell mass, resulting in embryonic lethality at the peri-implantation stage, indicating that SLD5 is essential for embryogenesis. Moreover, this phenotype of SLD5 mutant mice is quite similar compared with that of PSF1 mutant mice. We have previously reported that haploinsufficiency of PSF1 resulted in failure of acute proliferation of bone marrow hematopoietic stem cells (HSCs) during reconstitution of bone marrow ablated by 5-FU treatment. Since SLD5 was highly expressed in bone marrow, we investigated its involvement in bone marrow reconstitution after bone marrow ablation as observed in PSF1 heterozygous mutant mice. However, heterozygous deletion of the SLD5 gene was found not to significantly affect bone marrow reconstitution. On the other hand, abundant SLD5 expression was observed in human cancer cell lines and heterozygous deletion of the gene attenuated tumor progression in a murine model of spontaneous gastric cancer. These indicated that requirement and dependency of SLD5 for cell proliferation is different in different cell types.
Department of Signal Transduction, Research Institute for Microbial Diseases, Osaka University, Suita, Osaka, Japan ; Laboratory of Clinical Science and Biomedicine, Graduate School of Pharmaceutical Sciences, Osaka University, Suita, Osaka, Japan.
Tomomi
T
Mohri
Masaya
M
Ueno
Yumi
Y
Nagahama
Zhi-Yuan
ZY
Gong
Masahide
M
Asano
Hiroko
H
Oshima
Masanobu
M
Oshima
Yasushi
Y
Fujio
Nobuyuki
N
Takakura
D000071181:ATP Binding Cassette Transporter, Subfamily B, Member 2; D018528:ATP-Binding Cassette Transporters / Q000235:genetics / Q000378:metabolism; D000818:Animals; D002352:Carrier Proteins / Q000235:genetics / Q000378:metabolism*; D049109:Cell Proliferation; D047108:Embryonic Development; D005260:Female; D017353:Gene Deletion; D006801:Humans; D008297:Male; D051379:Mice; D008817:Mice, Mutant Strains
D000071181:ATP Binding Cassette Transporter, Subfamily B, Member 2; D018528:ATP-Binding Cassette Transporters; D002352:Carrier Proteins; C508079:SLD5 protein, mouse; C486171:Tap1 protein, mouse