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Scott Keeney
Memorial Sloan Kettering Cancer Center
139Publications
47H-index
9,361Citations
Publications 139
Newest
Published on Dec 1, 2019in Nature Communications11.88
Vijayalakshmi V. Subramanian5
Estimated H-index: 5
(NYU: New York University),
Xuan Zhu4
Estimated H-index: 4
(Amazon.com)
+ 5 AuthorsAndreas Hochwagen21
Estimated H-index: 21
(NYU: New York University)
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...
Published on Aug 24, 2019in Chromosoma3.53
Mehmet E. Karasu4
Estimated H-index: 4
(MSK: Memorial Sloan Kettering Cancer Center),
Scott Keeney47
Estimated H-index: 47
(MSK: Memorial Sloan Kettering Cancer Center)
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...
Published on Apr 1, 2019in Molecular Cell14.55
Michiel Boekhout2
Estimated H-index: 2
(MSK: Memorial Sloan Kettering Cancer Center),
Mehmet E. Karasu4
Estimated H-index: 4
(MSK: Memorial Sloan Kettering Cancer Center)
+ 8 AuthorsDinshaw J. Patel98
Estimated H-index: 98
(Cornell University)
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...
Published on Apr 1, 2019in Journal of Cell Biology8.89
Mehmet E. Karasu4
Estimated H-index: 4
(MSK: Memorial Sloan Kettering Cancer Center),
Nora Bouftas1
Estimated H-index: 1
(University of Paris)
+ 1 AuthorsKatja Wassmann14
Estimated H-index: 14
(University of Paris)
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...
Published on Jan 31, 2019in bioRxiv
Laurent Acquaviva2
Estimated H-index: 2
(MSK: Memorial Sloan Kettering Cancer Center),
Michiel Boekhout2
Estimated H-index: 2
(MSK: Memorial Sloan Kettering Cancer Center)
+ 7 AuthorsScott Keeney47
Estimated H-index: 47
(MSK: Memorial Sloan Kettering Cancer Center)
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...
Published on 2018in Nature Communications11.88
Sarai Pacheco5
Estimated H-index: 5
(Autonomous University of Barcelona),
Andros Maldonado-Linares3
Estimated H-index: 3
(Autonomous University of Barcelona)
+ 7 AuthorsOscar Fernandez-Capetillo40
Estimated H-index: 40
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...
Published on Dec 1, 2018in Nature Communications11.88
Carla M. Abreu2
Estimated H-index: 2
(MSK: Memorial Sloan Kettering Cancer Center),
Rohit Prakash4
Estimated H-index: 4
(MSK: Memorial Sloan Kettering Cancer Center)
+ 3 AuthorsMaria Jasin76
Estimated H-index: 76
(MSK: Memorial Sloan Kettering Cancer Center)
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 ...
Published on Sep 3, 2018in bioRxiv
Hajime Murakami8
Estimated H-index: 8
(MSK: Memorial Sloan Kettering Cancer Center),
Isabel Lam8
Estimated H-index: 8
(MSK: Memorial Sloan Kettering Cancer Center)
+ 2 AuthorsScott Keeney47
Estimated H-index: 47
(MSK: Memorial Sloan Kettering Cancer Center)
To segregate accurately during meiosis, homologous chromosomes in most species must recombine. Very small chromosomes would risk missegregation if recombination were randomly distributed, so the double-strand breaks (DSBs) that initiate recombination are not haphazard. How this nonrandomness is controlled is not understood. Here we demonstrate that Saccharomyces cerevisiae integrates multiple, temporally distinct pathways to regulate chromosomal binding of pro-DSB factors Rec114 and Mer2, thereb...
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