Germline mutations of BRCA1 are found in approximately half of familial breast cancer cases and the majority of kindreds with combined familial breast and ovary cancer (Alberg

Mammalian spermatogenesis proceeds through well-defined phases of mitotic and meiotic divisions as spermatogonia develop into spermatocytes, round spermatids and, finally, spermatozoa. In mice, all cell division in the testis is mitotic division before postnatal day 7 (P7). Starting from P8, spermatogonia enter the meiotic prophase of the meiotic pathway and homologous chromosomes undergo a programmed sequence of compaction, synapsis, recombination and segregation that leads to a reduction of genetic material from diploid to haploid (reviewed by Cohen and Pollard, 2001; Tarsounas and Moens, 2001; Zickler and Kleckner, 1999). A unique feature of meiosis I prophase chromatin is a high frequency of DNA double-strand breaks (DSBs), which are required for recombination between homologous chromosomes (reviewed by Cohen and Pollard, 2001; Roeder, 1997). Repair of DSBs is necessary to maintain genome integrity and limit the mutational potential of these breaks. Loss-of-function mutations of many factors involved in DNA damage repair result in defective spermatogenesis (reviewed by Cohen and Pollard, 2001; Dasika et al., 1999; Tarsounas and Moens, 2001). Germline mutations of BRCA1 are found in approximately half of familial breast cancer cases and the majority of kindreds with combined familial breast and ovary cancer (Alberg and Helzlsouer, 1997; Brody and Biesecker, 1998; Paterson, 1998). BRCA1 contains 24 exons that encode proteins of 1863 and 1812 amino acids in human and mouse, respectively (Lane et al., 1995; Miki et al., 1994). It has been shown that BRCA1 contains multiple functional domains that interact with numerous molecules including products of tumor suppressor genes, oncogenes, DNA damage-repair proteins, cell-cycle regulators, ubiquitin hydrolases, and transcriptional activators and repressors (reviewed by Deng and Brodie, 2000). These observations indicate that BRCA1 plays important roles in 2001 Development 130, 2001-2012 © 2003 The Company of Biologists Ltd doi:10.1242/dev.00410