The Roles of Spo11 and Sun1 in Novel Pre - DNA Double Strand Break Genome-wide Homology Search in Mammalian Meiosis

Thursday, October 11, 2012 — Poster Session III
10:00 a.m. – Noon	Natcher Conference Center, Building 45	NIDDK	GEN/GENOM-1

Authors

• K.A. Boateng
• M. A. Bellani
• I. V. Gregoretti
• F Pratto
• R. D. Camerini-Otero

Abstract

How homologous chromosomes (homologs) find their partner, establish an association (pairing) 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 neither dependent on its ability to make DSBs nor homologous recombination proteins. Intriguingly, SUN1, a protein required for telomere attachment to the nuclear envelope and for post-DSB synapsis occurring later in prophase I in mice, is also required for early pre-DSB homolog pairing. Furthermore, pre-DSB pairing at telomeres persists upon entry into prophase I, and is important for synapsis initiation. Our findings suggest that homologous recombination triggered by DSBs does not initiate a genome-wide search for homology, but rather proofreads and stabilizes the pre-DSB pairing of homologous chromosomes. In a nutshell, this finding fundamentally redraws the roles of DSB repair and recombination in meiosis.

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