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DNA Repair (Amst). 2018 Mar;63:25-38. doi: 10.1016/j.dnarep.2018.01.007. Epub 2018 Jan 31.

Repair of exogenous DNA double-strand breaks promotes chromosome synapsis in SPO11-mutant mouse meiocytes, and is altered in the absence of HORMAD1.

Author information

1
Department of Developmental Biology, Erasmus MC - University Medical Center, Rotterdam, The Netherlands.
2
Erasmus Optical Imaging Centre, Department of Pathology, Erasmus MC - University Medical Center, Rotterdam, The Netherlands.
3
Molecular Cell Biology Group/Experimental Center, Institute of Physiological Chemistry Medical School, MTZ, Dresden University of Technology, Dresden, Germany.
4
Department of Developmental Biology, Erasmus MC - University Medical Center, Rotterdam, The Netherlands. Electronic address: w.baarends@erasmusmc.nl.

Abstract

Repair of SPO11-dependent DNA double-strand breaks (DSBs) via homologous recombination (HR) is essential for stable homologous chromosome pairing and synapsis during meiotic prophase. Here, we induced radiation-induced DSBs to study meiotic recombination and homologous chromosome pairing in mouse meiocytes in the absence of SPO11 activity (Spo11YF/YF model), and in the absence of both SPO11 and HORMAD1 (Spo11/Hormad1 dko). Within 30 min after 5 Gy irradiation of Spo11YF/YF mice, 140-160 DSB repair foci were detected, which specifically localized to the synaptonemal complex axes. Repair of radiation-induced DSBs was incomplete in Spo11YF/YF compared to Spo11+/YF meiocytes. Still, repair of exogenous DSBs promoted partial recovery of chromosome pairing and synapsis in Spo11YF/YF meiocytes. This indicates that at least part of the exogenous DSBs can be processed in an interhomolog recombination repair pathway. Interestingly, in a seperate experiment, using 3 Gy of irradiation, we observed that Spo11/Hormad1 dko spermatocytes contained fewer remaining DSB repair foci at 48 h after irradiation compared to irradiated Spo11 knockout spermatocytes. Together, these results show that recruitment of exogenous DSBs to the synaptonemal complex, in conjunction with repair of exogenous DSBs via the homologous chromosome, contributes to homology recognition. In addition, the data suggest a role for HORMAD1 in DNA repair pathway choice in mouse meiocytes.

KEYWORDS:

DMC1; HORMAD1; Homologous recombination; Meiosis; RAD51; SPO11

PMID:
29414051
DOI:
10.1016/j.dnarep.2018.01.007
[Indexed for MEDLINE]
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