Match!
Julian Lange
Memorial Sloan Kettering Cancer Center
Homologous recombinationMeiosisSynapsisGeneticsBiology
33Publications
18H-index
3,165Citations
What is this?
Publications 26
Newest
#1Agnieszka Lukaszewicz (MSK: Memorial Sloan Kettering Cancer Center)H-Index: 1
#2Julian Lange (MSK: Memorial Sloan Kettering Cancer Center)H-Index: 18
Last. Maria Jasin (MSK: Memorial Sloan Kettering Cancer Center)H-Index: 64
view all 4 authors...
Numerous DNA double-strand breaks (DSBs) arise genome-wide during meiosis to ensure recombination between homologous chromosomes, which is required for gamete formation. The ATM kinase plays a central role in controlling both the number and position of DSBs, but the consequences of deregulated DSB formation have not been explored. Here we discovered that an unanticipated type of DNA deletion arises at meiotic recombination hotspots in the absence of ATM. Deletions form via joining of ends from t...
Source
#1Agnieszka Lukaszewicz (MSK: Memorial Sloan Kettering Cancer Center)H-Index: 1
#2Julian Lange (MSK: Memorial Sloan Kettering Cancer Center)H-Index: 18
Last. Maria Jasin (MSK: Memorial Sloan Kettering Cancer Center)H-Index: 8
view all 4 authors...
ABSTRACTDNA double-strand breaks (DSBs) generated by the SPO11 protein initiate meiotic recombination, an essential process for successful chromosome segregation during gametogenesis. The activity of SPO11 is controlled by multiple factors and regulatory mechanisms, such that the number of DSBs is limited and DSBs form at distinct positions in the genome and at the right time. Loss of this control can affect genome integrity or cause meiotic arrest by mechanisms that are not fully understood. He...
10 CitationsSource
#1Sarai Pacheco (Autonomous University of Barcelona)H-Index: 7
#2Andros Maldonado-Linares (Autonomous University of Barcelona)H-Index: 3
Last. Ignasi Roig (Autonomous University of Barcelona)H-Index: 19
view all 12 authors...
Precise execution of recombination during meiosis is essential for forming chromosomally-balanced gametes. Meiotic recombination initiates with the formation and resection of DNA double-strand breaks (DSBs). Cellular responses to meiotic DSBs are critical for efficient repair and quality control, but molecular features of these remain poorly understood, particularly in mammals. Here we report that the DNA damage response protein kinase ATR is crucial for meiotic recombination and completion of m...
15 CitationsSource
#1Alexander Widger (Francis Crick Institute)H-Index: 2
#2Shantha K. Mahadevaiah (Francis Crick Institute)H-Index: 35
Last. James M. A. Turner (Francis Crick Institute)H-Index: 36
view all 16 authors...
Meiotic cells undergo genetic exchange between homologs through programmed DNA double-strand break (DSB) formation, recombination and synapsis. In mice, the DNA damage-regulated phosphatidylinositol-3-kinase-like kinase (PIKK) ATM regulates all of these processes. However, the meiotic functions of the PIKK ATR have remained elusive, because germline-specific depletion of this kinase is challenging. Here we uncover roles for ATR in male mouse prophase I progression. ATR deletion causes chromosome...
18 CitationsSource
#1Alexander Widger (Francis Crick Institute)H-Index: 2
#2Shantha K. Mahadevaiah (Francis Crick Institute)H-Index: 35
Last. James M. A. Turner (Francis Crick Institute)H-Index: 36
view all 13 authors...
Meiotic cells undergo genetic exchange between homologous chromosomes through programmed DNA double-strand break (DSB) formation, recombination and synapsis [1, 2]. In mice, the DNA damage-regulated phosphatidylinositol-3-kinase-like kinase (PIKK) ATM regulates all of these processes [3-6]. However, the meiotic functions of another major PIKK, ATR, have remained elusive, because germ line-specific depletion of this kinase is challenging. Using an efficient conditional strategy, we uncover roles ...
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
#1Devanshi Jain (MSK: Memorial Sloan Kettering Cancer Center)H-Index: 4
#2Cem Meydan (Cornell University)H-Index: 17
Last. Scott Keeney (MSK: Memorial Sloan Kettering Cancer Center)H-Index: 53
view all 8 authors...
Transcriptional silencing by heritable cytosine-5 methylation is an ancient strategy to repress transposable elements. It was previously thought that mammals possess four DNA methyltransferase paralogs—Dnmt1, Dnmt3a, Dnmt3b and Dnmt3l—that establish and maintain cytosine-5 methylation. Here we identify a fifth paralog, Dnmt3c, that is essential for retrotransposon methylation and repression in the mouse male germline. From a phenotype-based forward genetics screen, we isolated a mutant mouse cal...
22 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
#1Devanshi Jain (MSK: Memorial Sloan Kettering Cancer Center)H-Index: 4
#2Cem Meydan (Cornell University)H-Index: 17
Last. Scott Keeney (MSK: Memorial Sloan Kettering Cancer Center)H-Index: 53
view all 7 authors...
Transcriptional silencing by heritable cytosine-5 methylation is an ancient strategy to repress transposable elements. It was previously thought that mammals possess four DNA methyltransferase paralogs — Dnmt1, Dnmt3a, Dnmt3b and Dnmt3l — that establish and maintain cytosine-5 methylation. Here we identify a fifth paralog, Dnmt3c, that is essential for retrotransposon methylation and repression in the mouse male germline. From a phenotype-based forward genetics screen, we isolated a mutant mouse...
2 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
123