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guylain

Guylain Boissonneault, Ph.D.

Professeur Titulaire

Université de Sherbrooke

Département de biochimie

Faculté de médecine et des sciences de la santé

Université de Sherbrooke

3201 rue Jean Mignault

Sherbrooke (Québec)

J1E 4K8 Canada

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Phone: 819 564-8000 ext. 75443

cell: 819-620-2146

 
 
 
Research Interests: 
  • Genetic instability of the haploid male germe cells
Summary of Results:
  • Most de novo transgenerational mutations are male-driven. We have shown that transient DNA double-stranded breaks are part of the differentiation program of spermatids. In such a haploid context, DNA repair must involves error-prone end-joining processes that should induce de novo mutations at break sites. We are currently generating the first genome-wide map of these transient breaks and will be investigating the mutation frequency at these sites which we hope will point to the origin of most male-driven de novo polymorphism. We have recently confirmed the genetic instability associated with the chromatin remodelling in spermatids by monitoring elongation of trinucleotide repeats within the Huntington’s disease gene. Our research is also aimed at understanding the global histone acetylation associated with the chromatin remodelling and the possible involvement of mitochondrial factors in this process.

 

Research Projects:
 
Stability of genetic information is of crucial importance for the normal function and reproduction of all living organisms. In heterogametic species, this stability must be maintained in somatic cells but also and most importantly in germline cells. Male and female gametes form the basis of every new individual, and their genomes’ integrity ensures faithful transmission of genetic information to the next generation. Recent data from the literature suggest that transmission of point mutations and chromosomal rearrangements arises from paternal origin. Although meiosis is a well-known source of genetic instability, our research activities over the past four years have focused on the haploid spermatids. Spermatids undergo a striking change in chromatin structure and our working hypothesis is that this important transition represents a major source of genetic instability that has probably been overlooked by reproductive biologists. We first established that elongating spermatids display DNA strand breaks that are part of the developmental program of these cells and may be required to support the change in DNA topology. Double-stranded breaks are being generated, and, given the haploid character of spermatids, these endogenous breaks cannot be repaired by homologous recombination but by an error-prone process related to the Non-Homologous End Joining (NHEJ). Hence, chromatin-remodeling steps in spermatids may be intrinsically mutagenic creating a slight genetic drift from one generation to the next without the need for exogenous genotoxic factors. Our goal is to determine the origin of the transient DNA strand breaks, their genome-wide distribution, their mutagenic potential, the DNA repair mechanism involved and the sensitivity of this transition to genotoxic agents such as those used for chemotherapy. Histone hyperacetylation is apparently necessary for the formation of DNA strand breaks and we identified a novel histone acetyltransferase with broad substrate specificity. We have set up a new technique for the genome-wide mapping of DNA strand breaks and are currently developing a strategy to determine subtle mutations induced by the transition process. Our recent immunofluorescence studies confirm that a DNA repair system compatible with NHEJ is present so that errors may be generated. We hope that this research program will confirm that this sensitive transition adds up to meiosis as a crucial determinant of genetic diversity with important consequences for evolution.
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Lab Members:
 
Name
Position
Email address
Marie-Chantal Gregoire
Ph.D.
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Olivier Simard
Ph.D.
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Julien Massonneau
M.Sc.
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Anne Gouraud
Ph.D.
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Marc-André Brazeau
M.Sc.
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List of Publications:
 

Gilbert, I., Bissonnette, N., Boissonneault, G., Vallee, M. and Robert C. A molecular analysis of the mRNA population in bovine spermatozoa. Reproduction, 133:1073-1086, 2007.

Leduc, F., Maquennehan, V., Bikond-Nkoma, G. and Boissonneault, G. DNA damage response during chromatin remodeling in elongating spermatids. Biology of Reproduction, 78: 324-332, 2008.

Leduc, F. Bikond-Nkoma, G. and Boissonneault, G. Spermiogenesis and DNA repair: A possible etiology of human infertility and genetic disorders. Systems Biology in Reproductive Medicine 54:3-10, 2008.

Bissonnette, N., Lévesque-Sergerie, J.P. and Boissonneault, G. Spermatozoal transcriptome profile as marker for bull fertility and sperm motility: A potential tool to evaluate semen quality. Reproduction, 138: 65-80, 2009.

Bikond-Nkoma, G., Leduc, F., Jaouad, L., and Boissonneault, G. Histone acetylation and DNA strand breaks in mouse elongating spermatids using a dual electron microscopy labeling approach. Andrologia, 42: 322-5, 2010.

Johnson, G.D., Lalancette, C, Linnemann, A., Leduc, F., Boissonneault, G, and Krawetz, S.A. The sperm nucleus: chromatin, RNA and the nuclear matrix. Reproduction. 141:21-36, 2011.

Leduc F, Faucher D, Bikond Nkoma G, Grégoire MC, Arguin M, Wellinger RJ, Boissonneault G., Genome-wide mapping of DNA strand breaks, PLoS One 6(2):e17353, 2011.

Boissonneault G. The genetic of sperm. International Innovation Report (Interview) 19:82-84, 2012.

Grégoire M.-C., Massonneau J. Simard O., Gouraud A., Brazeau M.-A., Arguin, M., Leduc, F. Boissonneault, G. Male-driven de novo mutations in haploid cells. Molecular Human Reproduction, 19(8):495-499, 2013.

Gouraud A., Brazeau M.-A., Grégoire M.-C., Simard O., Massonneau J., Arguin, M., Boissonneault G. Breaking news from spermatids. Basic and Clinical Andrology, 23:11, 2013.

 

Submitted refereed papers

Simard O., Grégoire M.-C, Brazeau, M.-A., Leduc, F., Marois, I., Richter, M., and Boissonneault, G. Genetic instability of the chromatin remodeling in spermatids. Nature Communications (Molecular Human Reproduction Submitted,) (CIHR-MOP93781)

Massonneau J., Arguin M., Grégoire M.-C., Dambreville C. and Boissonneault G. Quantitative determination of DNA 3’OH by qTUNEL. (DNA Repair Submitted) (CIHR-MOP93781)

 

Book chapters 

Grégoire M-C*, Leduc F*, Boissonneault G. Spermiogenesis in sperm genetic integrity. In : Sperm Chromatin: Biological and Clinical Application in Male Infertility and Assisted Reproduction. Humana Press. Co-editors : Dr Ashock Agarwal and Dr Armand Zini (2011).

Frédéric Leduc, Geneviève Acteau, Marie-Chantal Grégoire, Olivier Simard, Jessica Leroux, Audrey Carrier-Leclerc, Mélina Arguin and Guylain Boissonneault. Post-meiotic DNA damage and response in male germ cells In: DNA Repair/Book 4. INTECH open access publisher (2011).