Nuclear autoantigenic sperm protein (NASP), a linker histone chaperone that is required for cell proliferation.
A multichaperone nucleosome-remodeling complex that contains the H1 linker histone chaperone nuclear autoantigenic sperm protein (NASP) has recently been described. Linker histones (H1) are required for the proper completion of normal development, and NASP transports H1 histones into nuclei and exchanges H1 histones with DNA. Consequently, we investigated whether NASP is required for normal cell cycle progression and development. We now report that without sufficient NASP, HeLa cells and U2OS cells are unable to replicate their DNA and progress through the cell cycle and that the NASP(-/-) null mutation causes embryonic lethality. Although the null mutation NASP(-/-) caused embryonic lethality, null embryos survive until the blastocyst stage, which may be explained by the presence of stored NASP protein in the cytoplasm of oocytes. We conclude from this study that NASP and therefore the linker histones are key players in the assembly of chromatin after DNA replication.
Richardson
Richard T
RT
Department of Cell and Developmental Biology, University of North Carolina, Chapel Hill, North Carolina 27599-7090.
Alekseev
Oleg M
OM
Department of Cell and Developmental Biology, University of North Carolina, Chapel Hill, North Carolina 27599-7090.
Grossman
Gail
G
Department of Cell and Developmental Biology, University of North Carolina, Chapel Hill, North Carolina 27599-7090.
Widgren
Esther E
EE
Department of Cell and Developmental Biology, University of North Carolina, Chapel Hill, North Carolina 27599-7090.
Thresher
Randy
R
Program in Molecular Biology and Biotechnology, University of North Carolina, Chapel Hill, North Carolina 27599-7090.
Wagner
Eric J
EJ
Program in Molecular Biology and Biotechnology, University of North Carolina, Chapel Hill, North Carolina 27599-7090.
Sullivan
Kelly D
KD
Program in Molecular Biology and Biotechnology, University of North Carolina, Chapel Hill, North Carolina 27599-7090.
Marzluff
William F
WF
Program in Molecular Biology and Biotechnology, University of North Carolina, Chapel Hill, North Carolina 27599-7090.
O'Rand
Michael G
MG
Department of Cell and Developmental Biology, University of North Carolina, Chapel Hill, North Carolina 27599-7090. Electronic address: morand@unc.edu.
D000818:Animals; D001324:Autoantigens / Q000235:genetics* / Q000378:metabolism / Q000502:physiology*; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D004247:DNA / Q000737:chemistry; D005260:Female; D005822:Genetic Vectors; D005838:Genotype; D006367:HeLa Cells; D006657:Histones / Q000737:chemistry*; D006801:Humans; D051379:Mice; D008810:Mice, Inbred C57BL; D009154:Mutation; D009687:Nuclear Proteins / Q000235:genetics* / Q000378:metabolism / Q000502:physiology*
D001324:Autoantigens; D006657:Histones; C489390:NASP protein, human; D009687:Nuclear Proteins; D004247:DNA