QUICK SEARCH:   [advanced] Author: Keyword(s):
Home     Help     Feedback     Subscriptions     Archive     Search     Table of Contents

doi: 10.1242/10.1242/dev.00221

This Article Figures Only Full Text Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Hsia, K.-T. Articles by Saunders, P. T. K. Search for Related Content PubMed PubMed Citation Articles by Hsia, K.-T. Articles by Saunders, P. T. K. Social Bookmarking                         What's this?

DNA repair gene Ercc1 is essential for normal spermatogenesis and oogenesis and for functional integrity of germ cell DNA in the mouse

Kan-Tai Hsia^1,*, Michael R. Millar², Sasha King², Jim Selfridge¹, Nicola J. Redhead³, David W. Melton^3, and Philippa T. K. Saunders²

¹ Institute of Cell and Molecular Biology, University of Edinburgh, King's Buildings, Mayfield Road, Edinburgh EH9 3JR, UK
² MRC Human Reproductive Sciences Unit, Centre for Reproductive Biology, The Chancellor's Building, University of Edinburgh, 49 Little France Crescent, Edinburgh, EH16 4SB, UK
³ Sir Alastair Currie Cancer Research UK Laboratories, Molecular Medicine Centre, University of Edinburgh, Western General Hospital, Edinburgh EH4 2XU, UK
^* Present address: Faculty of Dentistry, National Yang-Ming University, Taiwan, ROC

Author for correspondence (e-mail: David.Melton{at}ed.ac.uk)

Accepted 23 October 2002

Ercc1 is essential for nucleotide excision repair (NER) but, unlike other NER proteins, Ercc1 and Xpf are also involved in recombination repair pathways. Ercc1 knockout mice have profound cell cycle abnormalities in the liver and die before weaning. Subsequently Xpa and Xpc knockouts have proved to be good models for the human NER deficiency disease, xeroderma pigmentosum, leading to speculation that the recombination, rather than the NER deficit is the key to the Ercc1 knockout phenotype. To investigate the importance of the recombination repair functions of Ercc1 we studied spermatogenesis and oogenesis in Ercc1-deficient mice. Male and female Ercc1-deficient mice were both infertile. Ercc1 was expressed at a high level in the testis and the highest levels of Ercc1 protein occurred in germ cells following meiotic crossing over. However, in Ercc1 null males some germ cell loss occurred prior to meiotic entry and there was no evidence that Ercc1 was essential for meiotic crossing over. An increased level of DNA strand breaks and oxidative DNA damage was found in Ercc1-deficient testis and increased apoptosis was noted in male germ cells. We conclude that the repair functions of Ercc1 are required in both male and female germ cells at all stages of their maturation. The role of endogenous oxidative DNA damage and the reason for the sensitivity of the germ cells to Ercc1 deficiency are discussed.

Key words: Meiosis, Nucleotide excision repair, Oxidative DNA damage, Recombination, Spermatozoa, Xeroderma pigmentosum

CiteULike    Complore    Connotea    Del.icio.us    Digg    Reddit    Technorati    Twitter    What's this?

This article has been cited by other articles:

				Y. Zhao and R. J. Epstein Programmed Genetic Instability: A Tumor-Permissive Mechanism for Maintaining the Evolvability of Higher Species through Methylation-Dependent Mutation of DNA Repair Genes in the Male Germ Line Mol. Biol. Evol., August 1, 2008; 25(8): 1737 - 1749. [Abstract] [Full Text] [PDF]

				C. Paul, D. W. Melton, and P. T.K. Saunders Do heat stress and deficits in DNA repair pathways have a negative impact on male fertility? Mol. Hum. Reprod., January 1, 2008; 14(1): 1 - 8. [Abstract] [Full Text] [PDF]

				L. O. Andrieux, A. Fautrel, A. Bessard, A. Guillouzo, G. Baffet, and S. Langouet GATA-1 Is Essential in EGF-Mediated Induction of Nucleotide Excision Repair Activity and ERCC1 Expression through ERK2 in Human Hepatoma Cells Cancer Res., March 1, 2007; 67(5): 2114 - 2123. [Abstract] [Full Text] [PDF]

				K.R. Barnett, C. Schilling, C.R. Greenfeld, D. Tomic, and J.A. Flaws Ovarian follicle development and transgenic mouse models Hum. Reprod. Update, September 1, 2006; 12(5): 537 - 555. [Abstract] [Full Text] [PDF]

				M. Fenech The Genome Health Clinic and Genome Health Nutrigenomics concepts: diagnosis and nutritional treatment of genome and epigenome damage on an individual basis Mutagenesis, July 1, 2005; 20(4): 255 - 269. [Abstract] [Full Text] [PDF]

				S. Banks, S. A King, D S. Irvine, and P. T K Saunders Impact of a mild scrotal heat stress on DNA integrity in murine spermatozoa Reproduction, April 1, 2005; 129(4): 505 - 514. [Abstract] [Full Text] [PDF]

				S. Diederichs, N. Baumer, P. Ji, S. K. Metzelder, G. E. Idos, T. Cauvet, W. Wang, M. Moller, S. Pierschalski, J. Gromoll, et al. Identification of Interaction Partners and Substrates of the Cyclin A1-CDK2 Complex J. Biol. Chem., August 6, 2004; 279(32): 33727 - 33741. [Abstract] [Full Text] [PDF]

				Ercc1-/- Mice (Ercc1tm1Dwm Mice) Sci. Aging Knowl. Environ., April 7, 2004; 2004(14): tg2 - tg2. [Full Text]