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Shintaro Yamada
Kyoto University
Homologous recombinationMeiosisPRDM9ChromatinCell biology
10Publications
5H-index
278Citations
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Publications 9
Newest
#1Shintaro Yamada (Kyoto University)H-Index: 5
#2Anjali Gupta Hinch (University of Oxford)H-Index: 5
Last. Scott Keeney (MSK: Memorial Sloan Kettering Cancer Center)H-Index: 53
view all 6 authors...
Exonucleolytic resection, critical to repair double-strand breaks (DSBs) by recombination, is not well understood, particularly in mammalian meiosis. Here, we define structures of resected DSBs in mouse spermatocytes genome-wide at nucleotide resolution. Resection tracts averaged 1100 nt, but with substantial fine-scale heterogeneity at individual hot spots. Surprisingly, EXO1 is not the major 5' --> 3' exonuclease, but the DSB-responsive kinase ATM proved a key regulator of both initiation and ...
6 CitationsSource
#1Remi Akagawa (Kyoto University)H-Index: 3
#2Hai Thanh Trinh (Kyoto University)H-Index: 1
Last. Shunichi Takeda (Kyoto University)H-Index: 77
view all 11 authors...
Summary Chemical modifications and adducts at DNA double-strand break (DSB) ends must be cleaned before re-joining by nonhomologous end-joining (NHEJ). MRE11 nuclease is essential for efficient removal of Topoisomerase II (TOP2)-DNA adducts from TOP2 poison-induced DSBs. However, mechanisms in MRE11 recruitment to DSB sites in G1 phase remain poorly understood. Here, we report that TOP2-DNA adducts are expeditiously removed through UBC13-mediated polyubiquitination, which promotes DSB resection ...
3 CitationsSource
#1Jacob Paiano (UPenn: University of Pennsylvania)H-Index: 3
#2Wei WuH-Index: 1
Last. Tanya T. Paull (University of Texas at Austin)H-Index: 46
view all 11 authors...
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 res...
12 CitationsSource
#1Jacob Paiano (UPenn: University of Pennsylvania)H-Index: 3
#1Jacob Paiano (NIH: National Institutes of Health)
Last. André Nussenzweig (NIH: National Institutes of Health)H-Index: 82
view all 11 authors...
Meiotic recombination is initiated by genome-wide SPO11-induced double-strand breaks (DSBs) that are processed by MRE11-mediated release of SPO11. The DSB is then resected and loaded with DMC1/RAD51 filaments that invade homologous chromosome templates. In most mammals, DSB locations (hotspots) are determined by the DNA sequence specificity of PRDM9. Here, we demonstrate the first direct detection of meiotic DSBs and resection in vertebrates by performing END-seq on mouse spermatocytes using low...
3 CitationsSource
#1Shintaro Yamada (Kyoto University)H-Index: 5
#2Anjali Gupta Hinch (University of Oxford)H-Index: 5
Last. Scott Keeney (MSK: Memorial Sloan Kettering Cancer Center)H-Index: 53
view all 6 authors...
Exonucleolytic resection, critical to repair double-strand breaks (DSBs) by recombination, is not well understood, particularly in mammalian meiosis. Here, we define structures of resected DSBs in mouse spermatocytes genome-wide at nucleotide resolution. Resection tracts averaged 1100 nucleotides, but with substantial fine-scale heterogeneity at individual hotspots. Surprisingly, EXO1 is not the major 5′→3′ exonuclease, but the DSB-responsive kinase ATM proved a key regulator of both initiation ...
2 CitationsSource
#1Shintaro Yamada (MSK: Memorial Sloan Kettering Cancer Center)H-Index: 5
#2Seoyoung Kim (MSK: Memorial Sloan Kettering Cancer Center)H-Index: 4
Last. Scott Keeney (MSK: Memorial Sloan Kettering Cancer Center)H-Index: 53
view all 6 authors...
ABSTRACTThe SPO11-generated DNA double-strand breaks (DSBs) that initiate meiotic recombination occur non-randomly across genomes, but mechanisms shaping their distribution and repair remain incompletely understood. Here, we expand on recent studies of nucleotide-resolution DSB maps in mouse spermatocytes. We find that trimethylation of histone H3 lysine 36 around DSB hotspots is highly correlated, both spatially and quantitatively, with trimethylation of H3 lysine 4, consistent with coordinated...
37 CitationsSource
#1Shintaro Yamada (MSK: Memorial Sloan Kettering Cancer Center)H-Index: 5
#2Seoyoung Kim (MSK: Memorial Sloan Kettering Cancer Center)H-Index: 4
Last. Scott Keeney (MSK: Memorial Sloan Kettering Cancer Center)H-Index: 53
view all 6 authors...
The SPO11-generated DNA double-strand breaks (DSBs) that initiate meiotic recombination occur non-randomly across genomes, but mechanisms shaping their distribution and repair remain incompletely understood. Here, we expand on recent studies of nucleotide-resolution DSB maps in mouse spermatocytes. We find that trimethylation of histone H3 lysine 36 around DSB hotspots is highly correlated, both spatially and quantitatively, with trimethylation of H3 lysine 4, consistent with coordinated formati...
4 CitationsSource
#1Eleni P. Mimitou (MSK: Memorial Sloan Kettering Cancer Center)H-Index: 9
#2Shintaro Yamada (MSK: Memorial Sloan Kettering Cancer Center)H-Index: 5
Last. Scott Keeney (MSK: Memorial Sloan Kettering Cancer Center)H-Index: 53
view all 3 authors...
Meiosis is a specialized double cell division that generates haploid gametes from diploid parent cells. Meiotic recombination between homologous chromosomes ensures the proper segregation of chromosomes to the daughter cells. Mimitou et al. carried out a genome-wide survey of resection of the ends of DNA double strand breaks in yeast. Resection generates single-stranded tails that are vital for meiotic recombination. The Tel1 kinase promoted initiation of resection. Nucleosomes, which normally p...
77 CitationsSource
#1Julian Lange (MSK: Memorial Sloan Kettering Cancer Center)H-Index: 18
#2Shintaro Yamada (MSK: Memorial Sloan Kettering Cancer Center)H-Index: 5
Last. Scott Keeney (Cornell University)H-Index: 53
view all 9 authors...
Summary Heritability and genome stability are shaped by meiotic recombination, which is initiated via hundreds of DNA double-strand breaks (DSBs). The distribution of DSBs throughout the genome is not random, but mechanisms molding this landscape remain poorly understood. Here, we exploit genome-wide maps of mouse DSBs at unprecedented nucleotide resolution to uncover previously invisible spatial features of recombination. At fine scale, we reveal a stereotyped hotspot structure—DSBs occur withi...
134 CitationsSource
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