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Poly(ADP-ribose) Metabolism Is Essential for Proper Nucleoprotein Exchange During Mouse Spermiogenesis

Lookup NU author(s): Dr Masafumi Ihara, Professor Caroline AustinORCiD

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Abstract

Sperm chromatin is organized in a protamine-based, highly condensed form, which protects the paternal chromosome complement in transit, facilitates fertilization, and supports correct gene expression in the early embryo. Very few histones remain selectively associated with genes and defined regulatory sequences essential to embryonic development, while most of the genome becomes bound to protamine during spermiogenesis. Chromatin remodeling processes resulting in the dramatically different nuclear structure of sperm are poorly understood. This study shows that perturbation of poly(ADPribose) (PAR) metabolism, which is mediated by PAR polymerases and PAR glycohydrolase in response to naturally occurring endogenous DNA strand breaks during spermatogenesis, results in the abnormal retention of core histones and histone linker HIST1H1T (H1t) and H1-like linker protein HILS1 in mature sperm. Moreover, genetic or pharmacological alteration of PAR metabolism caused poor sperm chromatin quality and an abnormal nuclear structure in mice, thus reducing male fertility.


Publication metadata

Author(s): Meyer-Ficca ML, Ihara M, Lonchar JD, Meistrich ML, Austin CA, Min W, Wang ZQ, Meyer RG

Publication type: Article

Publication status: Published

Journal: Biology of Reproduction

Year: 2011

Volume: 84

Issue: 2

Pages: 218-228

Print publication date: 29/09/2010

ISSN (print): 0006-3363

ISSN (electronic): 1529-7268

Publisher: Society for the Study of Reproduction

URL: http://dx.doi.org/10.1095/biolreprod.110.087361

DOI: 10.1095/biolreprod.110.087361


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Funding

Funder referenceFunder name
Mari Lowe Center for Comparative Oncology at the University of Pennsylvania
R01 HD48837National Institutes of Health (NIH)

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