**1. Introduction**

304 DNA Repair

Wright R.H.G., Dornan E.S., Donaldson M.M. & Morgan I.M. (2006). TopBP1 contains a

Xu Z.X., Timanova-Atanasova A., Zhao R.X. & Chang K.S. (2003). PML colocalizes with and

Yamane K., Chen J. & Kinsella T.J. (2003). Both DNA topoisomerase II-binding protein 1 and

Yamane K., Wu X. & Chen J. (2002). A DNA damage-regulated BRCT-containing protein,

Yamane K. & Tsuruo T. (1999). Conserved BRCT regions of TopBP1 and of the tumor

Yamane K., Kawabata M. & Tsuruo T. (1997). A DNA-topoisomerase-II – binding protein

Yan S. & Michael W.M. (2009). TopBP1 and DNA polymerase α-mediated recruitment of the

Yan S. & Michael W.M. (2009). TopBP1 and DNA polymerase-α directly recruit the 9-1-1

Yang X., Wood P.A. & Hrushesky W.J.M. (2010). Mammalian TIMELESS is required for

Yoo H.Y., Kumagai A., Shevchenko A., Schevchenko A. & Dunphy W.G. (2009). The Mre11-

Yoo H.Y., Kumagai A., Schevchenko A., Schevchenko A. & Dunphy W.G. (2007). Ataxia-

Yoshida K. & Inoue I. (2004). Expression of MCM10 and TopBP1 is regulated by cell

Zeng L., Hu Y. & Li B. (2005). Identification of TopBP1 as a c-Abl-interacting protein and a

*the Cell*, Vol. 20, No. 9, (May 2009), pp. 2351-2360, ISSN: 1059-1524

No. 24, (June 2007), pp. 17501-17506, ISSN: 0021-9258

37, (August 2004), pp. 6250-6260, ISSN: 0950-9232

(August 2005), pp. 29374-29380, ISSN: 0021-9258

*America*, Vol. 107, No. 31, (August 2010), pp. 13561-13562

Vol. 23, No. 12, (June 2003), pp. 4247-4256, ISSN: 0270-7306

(June 2003), pp. 3049-3053, ISSN: 0008-5472

(January 2002), pp. 555-566, ISSN: 0270-7306

794-799, ISSN: 0014-2956

2009), pp. 2877-2884, ISSN: 1551-4005

2008), pp. 907-915, ISSN: 1469-221X

(March 2009), pp. 793-804, ISSN: 0021-9525

37, (September 1999), pp. 5194-5203, ISSN: 0950-9232

transcriptional activation domain suppressed by two adjacent BRCT domains. *The Biochemical Journal*, Vol. 400, No. 3, (December 2006), pp. 573-582, ISSN: 0264-6021 Xu Y. & Leffak M. (2010). ATRIP from TopBP1 to ATR – *in vitro* activation of a DNA damage

checkpoint. *Proceedings of the National Academy of Science of the United States of* 

stabilizes the DNA damage response protein TopBP1. *Molecular and Cellular Biology*,

BRCA1 regulate the G2-M cell cycle checkpoint. *Cancer Research*, Vol. 63, No. 12,

TopBP1, is required for cell survival. *Molecular and Cellular Biology*, Vol. 22, No. 2,

suppressor BRCA1 bind strand breaks and termini of DNA. *Oncogene*, Vol. 18, No.

with eight repeating regions similar to DNA-repair enzymes and to a cell-cycle regulator. *European Journal of Biochemistry*, Vol. 250, No. 3, (December 1997), pp.

9-1-1 complex to stalled replication forks. *Cell Cycle*, Vol. 8, No. 18, (September

complex to stalled DNA replication forks. *The Journal of Cell Biology*, Vol. 184, No. 6,

ATM-dependent CHK2 activation and G2/M checkpoint control. *The Journal of Biological Chemistry*, Vol. 285, No. 5, (January 2010), pp. 3030-3034, ISSN: 0021-9258 Yang S.Z., Lin F.T. & Lin W.C. (2008). MCPH1/BRIT1 cooperates with E2F1 in the activation

of checkpoint, DNA repair and apoptosis. *EMBO Journal*, Vol. 9. No. 9, (September

Rad50-Nbs1 complex mediates activation of TopBP1 by ATM. *Molecular Biology of* 

telangiectasia mutated (ATM)-dependent activation of ATR occurs through phosphorylation of TopBP1 by ATM. *The Journal of Biological Chemistry*, Vol. 282,

proliferation and UV irradiation *via* E2F transcription factor. *Oncogene*, Vol. 23, No.

repressor for c-Abl expression. *The Journal of Biological Chemistry*, Vol. 280, No. 32,

Spermatids are haploid cells that differentiate into spermatozoa and may be considered as an interesting model of DNA damage response and repair. Key features, such a unique set of chromosomes, radioresistance to apoptosis, the presence of known end-joining DNA repair pathways and an underlying prerogative to limit the transmission of any mutation to the next generation, make them a unique cell type to provide new insights on similar pathways in somatic cells. Although DNA damage signaling and repair mechanisms have been extensively studied during meiosis, the contribution of post-meiotic germ cells to the genetic integrity of the male gamete have been overlooked. In this chapter we present clear evidences that the haploid phase of spermatogenesis, termed spermiogenesis, may represent an even greater challenge for the maintenance of the genetic integrity of the male gamete. Since transient DNA strand breaks are intrinsic to the differentiation program of spermatids (Leduc et al., 2008a; Marcon and Boissonneault, 2004), a better understanding of DNA repair pathways involved may shed some light on their potential contribution to male-driven *de novo* mutations and eventually to some unresolved cases of male infertility. This chapter will mainly focus on DNA breaks occurring in the post-meiotic phase of the spermatogenesis and how germ cells deal with it.
