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J. Biol. Chem., Vol. 281, Issue 30, 21526-21534, July 28, 2006

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Nuclear Autoantigenic Sperm Protein (NASP), a Linker Histone Chaperone That Is Required for Cell Proliferation^*

Richard T. Richardson, Oleg M. Alekseev, Gail Grossman, Esther E. Widgren, Randy Thresher, Eric J. Wagner¹, Kelly D. Sullivan, William F. Marzluff, and Michael G. O'Rand²

From the Department of Cell and Developmental Biology and the Program in Molecular Biology and Biotechnology, University of North Carolina, Chapel Hill, North Carolina 27599-7090

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.

Received for publication, April 20, 2006 , and in revised form, May 24, 2006.

^* This work was supported in part by NICHD, National Institutes of Health, through Cooperative Agreement U54HD35041 as part of the specialized cooperative centers program in reproductive research. The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked "advertisement" in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

¹ Supported by National Institutes of Health Grant F32 GM070101-02 and the Cottrell Foundation.

² To whom correspondence should be addressed: Department of Cell and Developmental Biology, CB#7090, University of North Carolina, Chapel Hill, NC 27599-7090. Tel.: 919-966-5698; Fax: 919-966-1856; E-mail: morand{at}unc.edu.

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