Publication Date:
2014-11-15
Description:
DNA double-strand breaks (DSBs) are introduced in meiosis to initiate recombination and generate crossovers, the reciprocal exchanges of genetic material between parental chromosomes. Here, we present high-resolution maps of meiotic DSBs in individual human genomes. Comparing DSB maps between individuals shows that along with DNA binding by PRDM9, additional factors may dictate the efficiency of DSB formation. We find evidence for both GC-biased gene conversion and mutagenesis around meiotic DSB hotspots, while frequent colocalization of DSB hotspots with chromosome rearrangement breakpoints implicates the aberrant repair of meiotic DSBs in genomic disorders. Furthermore, our data indicate that DSB frequency is a major determinant of crossover rate. These maps provide new insights into the regulation of meiotic recombination and the impact of meiotic recombination on genome function.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Pratto, Florencia -- Brick, Kevin -- Khil, Pavel -- Smagulova, Fatima -- Petukhova, Galina V -- Camerini-Otero, R Daniel -- 1R01GM084104-01A1/GM/NIGMS NIH HHS/ -- Intramural NIH HHS/ -- New York, N.Y. -- Science. 2014 Nov 14;346(6211):1256442. doi: 10.1126/science.1256442.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉National Institute of Diabetes, Digestive and Kidney Diseases, NIH, Bethesda, MD, USA. ; Department of Biochemistry and Molecular Biology, Uniformed Services University of Health Sciences, Bethesda, MD, USA. ; Department of Biochemistry and Molecular Biology, Uniformed Services University of Health Sciences, Bethesda, MD, USA. rdcamerini@mail.nih.gov galina.petukhova@usuhs.edu. ; National Institute of Diabetes, Digestive and Kidney Diseases, NIH, Bethesda, MD, USA. rdcamerini@mail.nih.gov galina.petukhova@usuhs.edu.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/25395542" target="_blank"〉PubMed〈/a〉
Keywords:
Alleles
;
*Chromosome Mapping
;
*DNA Breaks, Double-Stranded
;
Genome, Human/*genetics
;
*Genomic Instability
;
Histone-Lysine N-Methyltransferase/genetics/metabolism
;
*Homologous Recombination
;
Humans
;
Male
;
Meiosis/*genetics
;
Protein Binding
;
Spermatocytes
;
Telomere/genetics
Print ISSN:
0036-8075
Electronic ISSN:
1095-9203
Topics:
Biology
,
Chemistry and Pharmacology
,
Computer Science
,
Medicine
,
Natural Sciences in General
,
Physics
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