TY - JOUR
T1 - Homologous Pairing Preceding SPO11-Mediated Double-Strand Breaks in Mice
AU - Boateng, Kingsley A.
AU - Bellani, Marina A.
AU - Gregoretti, Ivan V.
AU - Pratto, Florencia
AU - Camerini-Otero, R. Daniel
N1 - Funding Information:
We thank M. Lichten (National Cancer Institute [NCI], NIH) and P. Hsieh (National Institute of Diabetes and Digestive and Kidney Diseases [NIDDK], NIH) for comments and discussion. We are also grateful to O. Voloshin, P. Khil, and G. Margolin (all from the NIDDK) for comments and help with data analysis. This work was supported by the NIDDK Intramural Research Program (to R.D.C.-O.).
PY - 2013/1/28
Y1 - 2013/1/28
N2 - 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.
AB - 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.
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U2 - 10.1016/j.devcel.2012.12.002
DO - 10.1016/j.devcel.2012.12.002
M3 - Article
C2 - 23318132
AN - SCOPUS:84873086796
SN - 1534-5807
VL - 24
SP - 196
EP - 205
JO - Developmental cell
JF - Developmental cell
IS - 2
ER -