Homologous Pairing Preceding SPO11-Mediated Double-Strand Breaks in Mice

• Published in: Developmental cell Vol. 24; no. 2; pp. 196 - 205
• Main Authors: Boateng, Kingsley A., Bellani, Marina A., Gregoretti, Ivan V., Pratto, Florencia, Camerini-Otero, R. Daniel
• Format: Journal Article
• Language: English
• Published: Cambridge, MA Elsevier Inc 28.01.2013; Cell Press
• Subjects: Animals; Biological and medical sciences; Cell differentiation, maturation, development, hematopoiesis; Cell physiology; Chromosome Pairing; Chromosomes; Chromosomes - metabolism; DNA; DNA Breaks, Double-Stranded; DNA damage; Endodeoxyribonucleases - genetics; Endodeoxyribonucleases - metabolism; Fundamental and applied biological sciences. Psychology; homologous recombination; Homology; Meiosis; Meiosis - genetics; Meiotic Prophase I - genetics; Mice; Microtubule-Associated Proteins - metabolism; Molecular and cellular biology; Nuclear membranes; Prophase; Telomere - metabolism; Telomeres; Double strand break; Vertebrata; Mammalia; Mouse; Rodentia; Development; Pairing
• ISSN: 1534-5807; 1878-1551
• DOI: 10.1016/j.devcel.2012.12.002

How homologous chromosomes (homologs) find their partner, pair, and recombine during meiosis constitutes the central phenomenon in eukaryotic genetics. It is widely believed that, in most organisms, SPO11-mediated DNA double-strand breaks (DSBs) introduced during prophase I precede and are required for efficient homolog pairing. We now show that, in the mouse, a significant level of homolog pairing precedes programmed DNA cleavage. Strikingly, this early chromosome pairing still requires SPO11 but is not dependent on its ability to make DSBs or homologous recombination proteins. Intriguingly, SUN1, a protein required for telomere attachment to the nuclear envelope and for post-DSB synapsis, is also required for early pre-DSB homolog pairing. Furthermore, pre-DSB pairing at telomeres persists upon entry into prophase I and is most likely important for initiation of synapsis. Our findings suggest that the DSB-triggered homology search may mainly serve to proofread and stabilize the pre-DSB pairing of homologous chromosomes. ► Homolog pairing precedes SPO11-mediated programmed DSBs during meiosis in the mouse ► A DSB-independent activity of SPO11 is required for this preleptotene pairing ► SUN1 anchors telomeres to the nuclear periphery to facilitate the pre-DSB pairing ► Pre-DSB subtelomeric pairing is more stable and most likely aids synapsis initiation DSB-independent meiotic pairing occurs in flies and worms, but its existence in yeast is controversial and has not been documented in mammals. Boateng et al. report pre-DSB meiotic pairing of homologous chromosomes in preleptotene mouse spermatocytes and show that these events require a DSB-independent function of SPO11 and SUN1.