Parp1–XRCC1 and the repair of DNA double strand breaks in mouse round spermatids

Ahmed, Emad A.; Boer, P. de; Philippens, M.E.P.; Kal, Henk B.; Rooij, Dirk G. de

doi:10.1016/j.mrfmmm.2009.10.011

Cited by 55 publications

(58 citation statements)

References 45 publications

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“…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.…”

Section: Discussionsupporting

confidence: 85%

“…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.…”

Section: Discussionmentioning

confidence: 99%

“…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.…”

Section: Introductionmentioning

confidence: 99%

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

Cordelli¹,

Eleuteri²,

Grollino³

et al. 2012

Environ and Mol Mutagen

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Sperm DNA integrity is essential for the accurate transmission of paternal genetic information. Various stages of spermatogenesis are characterized by large differences in radiosensitivity. Differentiating spermatogonia are susceptible to radiationinduced cell killing, but some of them can repair DNA damage and progress through differentiation. In this study, we applied the neutral comet assay, immunodetection of phosphorylated H2AX (g-H2AX) and the Sperm Chromatin Structure Assay (SCSA) to detect DNA strand breaks in testicular cells and spermatozoa at different times following in vivo X-ray irradiation. Radiation produced DNA strand breaks in testicular cells that were repaired within the first few hours after exposure. Spermatozoa were resistant to the induction of DNA damage, but non-targeted DNA lesions were detected in spermatozoa derived from surviving irradiated spermatogonia. These lesions formed while round spermatids started to elongate within the testicular seminiferous tubules. The transcription of pro-apoptotic genes at this time was also enhanced, suggesting that an apoptotic-like process was involved in DNA break production. Our results suggest that proliferating spermatogonia retain a memory of the radiation insult that is recognized at a later developmental stage and activates a process leading to DNA fragmentation. Environ. Mol. Mutagen. 53:429-439, 2012. V V C 2012 Wiley Periodicals, Inc.

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Section: Discussionsupporting

confidence: 85%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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

Cordelli¹,

Eleuteri²,

Grollino³

et al. 2012

Environ and Mol Mutagen

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“…Because removal of a single nucleosome structure induces one negative supercoil 56 , the accumulation of local negative supercoiling during the histoneprotamine transition period could induce an unusual cruciform conformation of the palindrome. Such massive histone removal may not occur in somatic cells, which could explain the spermspecific development of t(11;22)s. In mice, round spermatids were shown to have NHEJ activity 57 . On the other hand, a recent finding suggests that GEN1 acts in meiosis II, but it is still unclear whether the GEN1 also acts in post-meiotic cells or not 58 .…”

Section: Discussionmentioning

confidence: 99%

Two sequential cleavage reactions on cruciform DNA structures cause palindrome-mediated chromosomal translocations

et al. 2013

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Gross chromosomal rearrangements (GCRs), such as translocations, deletions or inversions, are often generated by illegitimate repair between two DNA breakages at regions with nucleotide sequences that might potentially adopt a non-B DNA conformation. We previously established a plasmid-based model system that recapitulates palindrome-mediated recurrent chromosomal translocations in humans, and demonstrated that cruciform DNA conformation is required for the translocation-like rearrangements. Here we show that two sequential reactions that cleave the cruciform structures give rise to the translocation: GEN1-mediated resolution that cleaves diagonally at the four-way junction of the cruciform and Artemismediated opening of the subsequently formed hairpin ends. Indeed, translocation products in human sperm reveal the remnants of this two-step mechanism. These two intrinsic pathways that normally fulfil vital functions independently, Holliday-junction resolution in homologous recombination and coding joint formation in rearrangement of antigen-receptor genes, act upon the unusual DNA conformation in concert and lead to a subset of recurrent GCRs in humans.

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“…However, some studies demonstrated that round spermatids are radioresistant to apoptosis and may not have the proper machinery and checkpoints to trigger such process (Ahmed et al, 2010;Oakberg and Diminno, 1960). Furthermore, our group have demonstrated that transient DNA breaks were present in the whole population of elongating spermatids of fertile mice and humans during chromatin remodeling and were therefore part of the normal differentiation program of these cells (Marcon and Boissonneault, 2004).…”

Section: Chromatin Remodeling Processmentioning

confidence: 97%