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Scott Keeney
Memorial Sloan Kettering Cancer Center
138Publications
51H-index
10.3kCitations
Publications 138
Newest
#1Vijayalakshmi V. Subramanian (NYU: New York University)H-Index: 6
#2Xuan Zhu (Amazon.com)H-Index: 6
Last.Andreas Hochwagen (NYU: New York University)H-Index: 21
view all 8 authors...
Faithful meiotic chromosome inheritance and fertility rely on the stimulation of meiotic crossover recombination by potentially genotoxic DNA double-strand breaks (DSBs). To avoid excessive damage, feedback mechanisms down-regulate DSBs, likely in response to initiation of crossover repair. In Saccharomyces cerevisiae, this regulation requires the removal of the conserved DSB-promoting protein Hop1/HORMAD during chromosome synapsis. Here, we identify privileged end-adjacent regions (EARs) spanni...
6 CitationsSource
#1Shaun E. Peterson (MSK: Memorial Sloan Kettering Cancer Center)H-Index: 2
#2Scott KeeneyH-Index: 51
Last.Maria JasinH-Index: 51
view all 3 authors...
Characteristics of heteroduplex DNA illuminate how strands exchange during homologous recombination, but mismatch correction can obscure them. To investigate recombination mechanisms, meiotic crossover products were analyzed at two hotspots in Msh2-/- mice containing homologous chromosomes derived from inbred strains. Recombination frequencies were unchanged in the mutant, implying that MSH2-dependent recombination suppression does not occur at this level of diversity. However, a substantial fra...
Source
#1Mehmet E. Karasu (MSK: Memorial Sloan Kettering Cancer Center)H-Index: 4
#2Scott Keeney (MSK: Memorial Sloan Kettering Cancer Center)H-Index: 51
Cyclins, as regulatory partners of cyclin-dependent kinases (CDKs), control the switch-like cell cycle transitions that orchestrate orderly duplication and segregation of genomes. Compared to mitosis, relatively little is known about how cyclin-CDK complexes control meiosis, the specialized cell division that generates gametes for sexual production. Mouse cyclin B3 was previously shown to have expression restricted to the beginning of meiosis, making it a candidate to regulate meiotic events. In...
1 CitationsSource
#1Michiel Boekhout (MSK: Memorial Sloan Kettering Cancer Center)H-Index: 2
#2Mehmet E. Karasu (MSK: Memorial Sloan Kettering Cancer Center)H-Index: 4
Last.Scott KeeneyH-Index: 51
view all 11 authors...
Summary Double-strand breaks (DSBs) initiate the homologous recombination that is crucial for meiotic chromosome pairing and segregation. Here, we unveil mouse ANKRD31 as a lynchpin governing multiple aspects of DSB formation. Spermatocytes lacking ANKRD31 have altered DSB locations and fail to target DSBs to the pseudoautosomal regions (PARs) of sex chromosomes. They also have delayed and/or fewer recombination sites but, paradoxically, more DSBs, suggesting DSB dysregulation. Unrepaired DSBs a...
6 CitationsSource
#1Mehmet E. Karasu (MSK: Memorial Sloan Kettering Cancer Center)H-Index: 4
#2Nora Bouftas (University of Paris)H-Index: 2
Last.Katja Wassmann (University of Paris)H-Index: 9
view all 4 authors...
Meiosis poses unique challenges because two rounds of chromosome segregation must be executed without intervening DNA replication. Mammalian cells express numerous temporally regulated cyclins, but how these proteins collaborate to control meiosis remains poorly understood. Here, we show that female mice genetically ablated for cyclin B3 are viable—indicating that the protein is dispensable for mitotic divisions—but are sterile. Mutant oocytes appear normal until metaphase I but then display a h...
9 CitationsSource
#1Laurent Acquaviva (MSK: Memorial Sloan Kettering Cancer Center)H-Index: 2
#2Michiel Boekhout (MSK: Memorial Sloan Kettering Cancer Center)H-Index: 2
Last.Scott Keeney (MSK: Memorial Sloan Kettering Cancer Center)H-Index: 51
view all 10 authors...
Sex chromosomes in males share only a diminutive homologous segment, the pseudoautosomal region (PAR), wherein meiotic double-strand breaks (DSBs), pairing, and crossing over must occur for correct segregation. How cells ensure PAR recombination is unknown. Here we delineate cis- and trans-acting factors that control PAR ultrastructure and make the PAR the hottest area of DSB formation in the male mouse genome. Prior to DSB formation, PAR chromosome axes elongate, sister chromatids separate, and...
4 CitationsSource
#1Sarai Pacheco (Autonomous University of Barcelona)H-Index: 6
#2Andros Maldonado-Linares (Autonomous University of Barcelona)H-Index: 3
Last.Ignasi Roig (Autonomous University of Barcelona)H-Index: 18
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...
9 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...
9 CitationsSource
#1Carla Manuela Abreu (MSK: Memorial Sloan Kettering Cancer Center)H-Index: 4
#2Rohit Prakash (MSK: Memorial Sloan Kettering Cancer Center)H-Index: 5
Last.Maria Jasin (MSK: Memorial Sloan Kettering Cancer Center)H-Index: 51
view all 6 authors...
The DNA-damage repair pathway homologous recombination (HR) requires factors that promote the activity of strand-exchange protein RAD51 and its meiosis-specific homolog DMC1. Here we show that the Shu complex SWS1-SWSAP1, a candidate for one such HR regulator, is dispensable for mouse viability but essential for male and female fertility, promoting the assembly of RAD51 and DMC1 on early meiotic HR intermediates. Only a fraction of mutant meiocytes progress to form crossovers, which are crucial ...
9 CitationsSource
#1Michiel Boekhout (MSK: Memorial Sloan Kettering Cancer Center)H-Index: 2
#2Mehmet E. Karasu (MSK: Memorial Sloan Kettering Cancer Center)H-Index: 4
Last.Scott Keeney (MSK: Memorial Sloan Kettering Cancer Center)H-Index: 51
view all 10 authors...
Double-strand breaks (DSBs) initiate the homologous recombination that is crucial for meiotic chromosome pairing and segregation. Here we unveil mouse ANKRD31 as a lynchpin governing multiple aspects of DSB formation. Spermatocytes lacking ANKRD31 have altered DSB locations and fail to target DSBs to sex chromosomes' pseudoautosomal regions (PAR). They also have delayed/fewer recombination sites but, paradoxically, more DSBs, suggesting DSB dysregulation. Unrepaired DSBs and pairing failures--st...
1 CitationsSource
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