Differences in DNA double strand breaks repair in male germ cell types: Lessons learned from a differential expression of Mdc1 and 53BP1

Direct and delayed X‐ray‐induced DNA damage in male mouse germ cells

“…These results are in agreement with the known decrease in radiosensitivity of maturing male germ cells, which has been linked to chromatin condensation and replacement of histones with protamines in these cells [Joshi et al, 1990;van Loon et al, 1993;Haines et al, 1998]. In addition, they reflect the proficiency of testicular cells in both Non Homologous End Joining (NHEJ) and Homologous Recombination (HR)-mediated repair [Srivastava and Raman, 2007;Ahmed et al, 2007Ahmed et al, , 2010a. Despite the initial repair of DNA damage in testicular cells, a subsequent time-course analysis of DNA damage between 7 and 45 days after irradiation revealed the appearance of delayed DNA lesions in both testicular cells and sperm.…”

“…Phosphorylated H2AX (g-H2AX) foci are markers of DNA double strand breaks [Rogakou et al, 1998]. g-H2AX content in testicular cells is heterogeneous, higher than in cells from other organs and increases after irradiation [Hamer et al, 2003;Ahmed et al, 2007Ahmed et al, , 2010aBlanco-Rodriguez, 2009;Paris et al, 2011]. The presence of H2AX has been documented in human [Gatewood et al, 1990] and in mouse [Meyer-Ficca et al, 2009] sperm chromatin.…”

“…Nevertheless, it is interesting to speculate whether there is a common denominator between differentiating spermatogonia and early meiotic cells that may be affecting their susceptibility to radiation-induced delayed effects. Proliferating spermatogonia have several features that define them as a unique testicular subpopulation: replicative DNA synthesis, mitotic activity, chromatin organization, DNA repair pathways, and radiosensitivity [van der Meer et al, 1992;Ahmed et al, 2007;Rube et al, 2011]. DNA synthesis also occurs in preleptotene spermatocytes, and in zygotene/ pachytene spermatocytes where it is associated with the repair of double strand breaks introduced during the homology search process [Kidane et al, 2010].…”

“…The sensitivity of male germ cells to ionizing radiation depends on the differentiation stage, chromatin condensation, nucleoproteins composition, and variation in repair capacity at the time of exposure [Spanò et al, 1987;Beumer et al, 1997;Ahmed et al, 2007Ahmed et al, , 2010a. Direct ionization of cellular macromolecules, particularly DNA, or indirect damage to these macromolecules via reactive oxygen species produced by water radiolysis, can cause cell death, DNA damage, chromosome aberrations, and mutations.…”

DNA double strand break repair, chromosome synapsis and transcriptional silencing in meiosis

“…These include BRCA1, BRCA2, BLM, MDC1, TOPBP1, 53BP1 and RAD1. [102][103][104][105][106][107][108] The above-mentioned post replication repair enzyme HR6B and its E3 ligase partner RAD18 also accumulate on the XY body. 109 All of these proteins, except BLM, 53BP1 and the RAD18/ HR6A/B complex, also accumulate on the meiotic DSBs shortly after their formation in leptotene.…”