ATM and PRDM9 regulate SPO11-bound recombination intermediates during meiosis.
Animals
Ataxia Telangiectasia Mutated Proteins
/ genetics
BRCA1 Protein
/ genetics
Cell Cycle Proteins
/ genetics
Chromatin
DNA Repair Enzymes
/ genetics
Endodeoxyribonucleases
/ genetics
Exodeoxyribonucleases
/ genetics
Female
Histone-Lysine N-Methyltransferase
/ genetics
Homologous Recombination
/ physiology
MRE11 Homologue Protein
/ metabolism
Male
Meiosis
/ physiology
Mice
Mice, Inbred C57BL
Mice, Knockout
Phosphate-Binding Proteins
/ genetics
Spermatocytes
/ metabolism
Tumor Suppressor p53-Binding Protein 1
/ genetics
Journal
Nature communications
ISSN: 2041-1723
Titre abrégé: Nat Commun
Pays: England
ID NLM: 101528555
Informations de publication
Date de publication:
12 02 2020
12 02 2020
Historique:
received:
24
12
2019
accepted:
23
01
2020
entrez:
14
2
2020
pubmed:
14
2
2020
medline:
24
4
2020
Statut:
epublish
Résumé
Meiotic recombination is initiated by SPO11-induced double-strand breaks (DSBs). In most mammals, the methyltransferase PRDM9 guides SPO11 targeting, and the ATM kinase controls meiotic DSB numbers. Following MRE11 nuclease removal of SPO11, the DSB is resected and loaded with DMC1 filaments for homolog invasion. Here, we demonstrate the direct detection of meiotic DSBs and resection using END-seq on mouse spermatocytes with low sample input. We find that DMC1 limits both minimum and maximum resection lengths, whereas 53BP1, BRCA1 and EXO1 play surprisingly minimal roles. Through enzymatic modifications to END-seq, we identify a SPO11-bound meiotic recombination intermediate (SPO11-RI) present at all hotspots. We propose that SPO11-RI forms because chromatin-bound PRDM9 asymmetrically blocks MRE11 from releasing SPO11. In Atm
Identifiants
pubmed: 32051414
doi: 10.1038/s41467-020-14654-w
pii: 10.1038/s41467-020-14654-w
pmc: PMC7016097
doi:
Substances chimiques
BRCA1 Protein
0
Brca1 protein, mouse
0
Cell Cycle Proteins
0
Chromatin
0
Dmc1 protein, mouse
0
Mre11a protein, mouse
0
Phosphate-Binding Proteins
0
Trp53bp1 protein, mouse
0
Tumor Suppressor p53-Binding Protein 1
0
Histone-Lysine N-Methyltransferase
EC 2.1.1.43
prdm9 protein, mouse
EC 2.1.1.43
Ataxia Telangiectasia Mutated Proteins
EC 2.7.11.1
Atm protein, mouse
EC 2.7.11.1
Endodeoxyribonucleases
EC 3.1.-
Exo1 protein, mouse
EC 3.1.-
Exodeoxyribonucleases
EC 3.1.-
MRE11 Homologue Protein
EC 3.1.-
meiotic recombination protein SPO11
EC 3.1.-
DNA Repair Enzymes
EC 6.5.1.-
Types de publication
Journal Article
Research Support, N.I.H., Intramural
Research Support, Non-U.S. Gov't
Research Support, U.S. Gov't, Non-P.H.S.
Langues
eng
Sous-ensembles de citation
IM
Pagination
857Subventions
Organisme : NCI NIH HHS
ID : P30 CA008748
Pays : United States
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