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Pictured is the immunofluorescent staining of 2-month-old ovarian sections showing increased γH2AX in PP6c-depleted oocytes. Blue is DAPI stain. Green is immunofluorescence signal of γH2AX, a marker of DNA double strand breaks. Red is immunofluorescence signal of MVH (mouse VASA homolog), a germ cell marker. Using a genetically modified mouse model with specific deletion of Ppp6c in oocytes from the primordial follicle stage, we show that PP6 plays a critical role in germ cell survival and follicular development by safeguarding the genomic integrity of prophase I-arrested oocytes. See Hu, Meng et al.

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Image Credit: Meng-Wen Hu

Editorial

Bringing PLOS Genetics Editors to Preprint Servers

Gregory S. Barsh, Casey M. Bergman, Christopher D. Brown, Nadia D. Singh, Gregory P. Copenhaver

PLOS Genetics: published December 1, 2016 | https://doi.org/10.1371/journal.pgen.1006448

Perspectives

Middle Age Has Its Advantages

Maureen M. Barr

PLOS Genetics: published December 1, 2016 | https://doi.org/10.1371/journal.pgen.1006426

Craniofacial Ciliopathies and the Interpretation of Hedgehog Signal Transduction

Karen J. Liu

PLOS Genetics: published December 29, 2016 | https://doi.org/10.1371/journal.pgen.1006460

A Hox-Embedded Long Noncoding RNA: Is It All Hot Air?

Licia Selleri, Marisa S. Bartolomei, Wendy A. Bickmore, Lin He, Lisa Stubbs, Wolf Reik, Gregory S. Barsh

PLOS Genetics: published December 15, 2016 | https://doi.org/10.1371/journal.pgen.1006485

Review

Tumor Suppressor Genes within Common Fragile Sites Are Active Players in the DNA Damage Response

Idit Hazan, Thomas G. Hofmann, Rami I. Aqeilan

PLOS Genetics: published December 15, 2016 | https://doi.org/10.1371/journal.pgen.1006436

Research Articles

Hotair Is Dispensible for Mouse Development

Ana Rita Amândio, Anamaria Necsulea, Elisabeth Joye, Bénédicte Mascrez, Denis Duboule

PLOS Genetics: published December 15, 2016 | https://doi.org/10.1371/journal.pgen.1006232

Structural and Functional Recovery of Sensory Cilia in C. elegans IFT Mutants upon Aging

Astrid Cornils, Ashish K. Maurya, Lauren Tereshko, Julie Kennedy, Andrea G. Brear, Veena Prahlad, Oliver E. Blacque, Piali Sengupta

PLOS Genetics: published December 1, 2016 | https://doi.org/10.1371/journal.pgen.1006325

The Jujube Genome Provides Insights into Genome Evolution and the Domestication of Sweetness/Acidity Taste in Fruit Trees

Jian Huang, Chunmei Zhang, Xing Zhao, Zhangjun Fei, KangKang Wan, Zhong Zhang, Xiaoming Pang, Xiao Yin, Yang Bai, Xiaoqing Sun, Lizhi Gao, Ruiqiang Li, Jinbo Zhang, Xingang Li

PLOS Genetics: published December 22, 2016 | https://doi.org/10.1371/journal.pgen.1006433

The Gene Regulatory Network of Lens Induction Is Wired through Meis-Dependent Shadow Enhancers of Pax6

Barbora Antosova, Jana Smolikova, Lucie Klimova, Jitka Lachova, Michaela Bendova, Iryna Kozmikova, Ondrej Machon, Zbynek Kozmik

PLOS Genetics: published December 5, 2016 | https://doi.org/10.1371/journal.pgen.1006441

A Bystander Mechanism Explains the Specific Phenotype of a Broadly Expressed Misfolded Protein

Lauren Klabonski, Ji Zha, Lakshana Senthilkumar, Tali Gidalevitz

PLOS Genetics: published December 7, 2016 | https://doi.org/10.1371/journal.pgen.1006450

A Novel Rrm3 Function in Restricting DNA Replication via an Orc5-Binding Domain Is Genetically Separable from Rrm3 Function as an ATPase/Helicase in Facilitating Fork Progression

Salahuddin Syed, Claus Desler, Lene J. Rasmussen, Kristina H. Schmidt

PLOS Genetics: published December 6, 2016 | https://doi.org/10.1371/journal.pgen.1006451

Investigating Conservation of the Cell-Cycle-Regulated Transcriptional Program in the Fungal Pathogen, Cryptococcus neoformans

Christina M. Kelliher, Adam R. Leman, Crystal S. Sierra, Steven B. Haase

PLOS Genetics: published December 5, 2016 | https://doi.org/10.1371/journal.pgen.1006453

Bilaterian Giant Ankyrins Have a Common Evolutionary Origin and Play a Conserved Role in Patterning the Axon Initial Segment

Timothy Jegla, Michelle M. Nguyen, Chengye Feng, Daniel J. Goetschius, Esteban Luna, Damian B. van Rossum, Bishoy Kamel, Aditya Pisupati, Elliott S. Milner, Melissa M. Rolls

PLOS Genetics: published December 2, 2016 | https://doi.org/10.1371/journal.pgen.1006457

Chronological Lifespan in Yeast Is Dependent on the Accumulation of Storage Carbohydrates Mediated by Yak1, Mck1 and Rim15 Kinases

Lu Cao, Yingzhi Tang, Zhenzhen Quan, Zhe Zhang, Stephen G. Oliver, Nianshu Zhang

PLOS Genetics: published December 6, 2016 | https://doi.org/10.1371/journal.pgen.1006458

Mutations in the Heme Exporter FLVCR1 Cause Sensory Neurodegeneration with Loss of Pain Perception

Deborah Chiabrando, Marco Castori, Maja di Rocco, Martin Ungelenk, Sebastian Gießelmann, Matteo Di Capua, Annalisa Madeo, Paola Grammatico, Sophie Bartsch, Christian A. Hübner, Fiorella Altruda, Lorenzo Silengo, Emanuela Tolosano, Ingo Kurth

PLOS Genetics: published December 6, 2016 | https://doi.org/10.1371/journal.pgen.1006461

Retinal Expression of the Drosophila eyes absent Gene Is Controlled by Several Cooperatively Acting Cis-regulatory Elements

Bonnie M. Weasner, Brandon P. Weasner, Sarah D. Neuman, Arash Bashirullah, Justin P. Kumar

PLOS Genetics: published December 8, 2016 | https://doi.org/10.1371/journal.pgen.1006462

The Mitochondrial m-AAA Protease Prevents Demyelination and Hair Greying

Shuaiyu Wang, Julie Jacquemyn, Sara Murru, Paola Martinelli, Esther Barth, Thomas Langer, Carien M. Niessen, Elena I. Rugarli

PLOS Genetics: published December 2, 2016 | https://doi.org/10.1371/journal.pgen.1006463

Alternative Splicing within and between Drosophila Species, Sexes, Tissues, and Developmental Stages

Lauren Gibilisco, Qi Zhou, Shivani Mahajan, Doris Bachtrog

PLOS Genetics: published December 9, 2016 | https://doi.org/10.1371/journal.pgen.1006464

PCNA-Dependent Cleavage and Degradation of SDE2 Regulates Response to Replication Stress

Ukhyun Jo, Winson Cai, Jingming Wang, Yoojin Kwon, Alan D. D’Andrea, Hyungjin Kim

PLOS Genetics: published December 1, 2016 | https://doi.org/10.1371/journal.pgen.1006465

The Transcription Factor Nfatc2 Regulates β-Cell Proliferation and Genes Associated with Type 2 Diabetes in Mouse and Human Islets

Mark P. Keller, Pradyut K. Paul, Mary E. Rabaglia, Donnie S. Stapleton, Kathryn L. Schueler, Aimee Teo Broman, Shuyun Isabella Ye, Ning Leng, Christopher J. Brandon, Elias Chaibub Neto, Christopher L. Plaisier, Shane P. Simonett, Melkam A. Kebede, Gloria M. Sheynkman, Mark A. Klein, Nitin S. Baliga, Lloyd M. Smith, Karl W. Broman, Brian S. Yandell, Christina Kendziorski, Alan D. Attie

PLOS Genetics: published December 9, 2016 | https://doi.org/10.1371/journal.pgen.1006466

Allelic Variation in CXCL16 Determines CD3⁺ T Lymphocyte Susceptibility to Equine Arteritis Virus Infection and Establishment of Long-Term Carrier State in the Stallion

Sanjay Sarkar, Ernest Bailey, Yun Young Go, R. Frank Cook, Ted Kalbfleisch, John Eberth, R. Lakshman Chelvarajan, Kathleen M. Shuck, Sergey Artiushin, Peter J. Timoney, Udeni B. R. Balasuriya

PLOS Genetics: published December 8, 2016 | https://doi.org/10.1371/journal.pgen.1006467

Identification of a Novel L-rhamnose Uptake Transporter in the Filamentous Fungus Aspergillus niger

Jasper Sloothaak, Dorett I. Odoni, Vitor A. P. Martins dos Santos, Peter J. Schaap, Juan Antonio Tamayo-Ramos

PLOS Genetics: published December 16, 2016 | https://doi.org/10.1371/journal.pgen.1006468

Whole-Organism Developmental Expression Profiling Identifies RAB-28 as a Novel Ciliary GTPase Associated with the BBSome and Intraflagellar Transport

Victor L. Jensen, Stephen Carter, Anna A. W. M. Sanders, Chunmei Li, Julie Kennedy, Tiffany A. Timbers, Jerry Cai, Noemie Scheidel, Breandán N. Kennedy, Ryan D. Morin, Michel R. Leroux, Oliver E. Blacque

PLOS Genetics: published December 8, 2016 | https://doi.org/10.1371/journal.pgen.1006469

Comparative Transcriptomic and Epigenomic Analyses Reveal New Regulators of Murine Brown Adipogenesis

Reinhard Brunmeir, Jingyi Wu, Xu Peng, Sun-Yee Kim, Sofi G. Julien, Qiongyi Zhang, Wei Xie, Feng Xu

PLOS Genetics: published December 6, 2016 | https://doi.org/10.1371/journal.pgen.1006474

The C. elegans Discoidin Domain Receptor DDR-2 Modulates the Met-like RTK–JNK Signaling Pathway in Axon Regeneration

Naoki Hisamoto, Yuki Nagamori, Tatsuhiro Shimizu, Strahil I. Pastuhov, Kunihiro Matsumoto

PLOS Genetics: published December 16, 2016 | https://doi.org/10.1371/journal.pgen.1006475

Gene Expression Differences in Prostate Cancers between Young and Old Men

Yuanchun Ding, Huiqing Wu, Charles Warden, Linda Steele, Xueli Liu, M. van Iterson, Xiwei Wu, Rebecca Nelson, Zheng Liu, Yate-Ching Yuan, Susan L. Neuhausen

PLOS Genetics: published December 27, 2016 | https://doi.org/10.1371/journal.pgen.1006477

Ku Binding on Telomeres Occurs at Sites Distal from the Physical Chromosome Ends

Mélanie V. Larcher, Emeline Pasquier, R. Stephen MacDonald, Raymund J. Wellinger

PLOS Genetics: published December 8, 2016 | https://doi.org/10.1371/journal.pgen.1006479

A Point Mutation in a lincRNA Upstream of GDNF Is Associated to a Canine Insensitivity to Pain: A Spontaneous Model for Human Sensory Neuropathies

Jocelyn Plassais, Laetitia Lagoutte, Solenne Correard, Manon Paradis, Eric Guaguère, Benoit Hédan, Alix Pommier, Nadine Botherel, Marie-Christine Cadiergues, Philippe Pilorge, David Silversides, Maud Bizot, Mark Samuels, Carme Arnan, Rory Johnson, Christophe Hitte, Gilles Salbert, Agnès Méreau, Pascale Quignon, Thomas Derrien, Catherine André

PLOS Genetics: published December 29, 2016 | https://doi.org/10.1371/journal.pgen.1006482

Loss of RMI2 Increases Genome Instability and Causes a Bloom-Like Syndrome

Damien F. Hudson, David J. Amor, Amber Boys, Kathy Butler, Lorna Williams, Tao Zhang, Paul Kalitsis

PLOS Genetics: published December 15, 2016 | https://doi.org/10.1371/journal.pgen.1006483

GW182-Free microRNA Silencing Complex Controls Post-transcriptional Gene Expression during Caenorhabditis elegans Embryogenesis

Guillaume Jannot, Pascale Michaud, Miguel Quévillon Huberdeau, Louis Morel-Berryman, James A. Brackbill, Sandra Piquet, Katherine McJunkin, Kotaro Nakanishi, Martin J. Simard

PLOS Genetics: published December 9, 2016 | https://doi.org/10.1371/journal.pgen.1006484

Phosphatidylserine Ameliorates Neurodegenerative Symptoms and Enhances Axonal Transport in a Mouse Model of Familial Dysautonomia

Shiran Naftelberg, Ziv Abramovitch, Shani Gluska, Sivan Yannai, Yuvraj Joshi, Maya Donyo, Keren Ben-Yaakov, Tal Gradus, Jonathan Zonszain, Chen Farhy, Ruth Ashery-Padan, Eran Perlson, Gil Ast

PLOS Genetics: published December 20, 2016 | https://doi.org/10.1371/journal.pgen.1006486

Bypass of Candida albicans Filamentation/Biofilm Regulators through Diminished Expression of Protein Kinase Cak1

Carol A. Woolford, Katherine Lagree, Wenjie Xu, Tatyana Aleynikov, Hema Adhikari, Hiram Sanchez, Paul J. Cullen, Frederick Lanni, David R. Andes, Aaron P. Mitchell

PLOS Genetics: published December 9, 2016 | https://doi.org/10.1371/journal.pgen.1006487

Unique Function of the Bacterial Chromosome Segregation Machinery in Apically Growing Streptomyces - Targeting the Chromosome to New Hyphal Tubes and its Anchorage at the Tips

Agnieszka Kois-Ostrowska, Agnieszka Strzałka, Natalia Lipietta, Emma Tilley, Jolanta Zakrzewska-Czerwińska, Paul Herron, Dagmara Jakimowicz

PLOS Genetics: published December 15, 2016 | https://doi.org/10.1371/journal.pgen.1006488

Mutation Rate Variation is a Primary Determinant of the Distribution of Allele Frequencies in Humans

Arbel Harpak, Anand Bhaskar, Jonathan K. Pritchard

PLOS Genetics: published December 15, 2016 | https://doi.org/10.1371/journal.pgen.1006489

Transcriptional Orchestration of the Global Cellular Response of a Model Pennate Diatom to Diel Light Cycling under Iron Limitation

Sarah R. Smith, Jeroen T. F. Gillard, Adam B. Kustka, John P. McCrow, Jonathan H. Badger, Hong Zheng, Ashley M. New, Chris L. Dupont, Toshihiro Obata, Alisdair R. Fernie, Andrew E. Allen

PLOS Genetics: published December 14, 2016 | https://doi.org/10.1371/journal.pgen.1006490

Winner's Curse Correction and Variable Thresholding Improve Performance of Polygenic Risk Modeling Based on Genome-Wide Association Study Summary-Level Data

Jianxin Shi, Ju-Hyun Park, Jubao Duan, Sonja T. Berndt, Winton Moy, Kai Yu, Lei Song, William Wheeler, Xing Hua, Debra Silverman, Montserrat Garcia-Closas, Chao Agnes Hsiung, Jonine D. Figueroa, Victoria K. Cortessis, Núria Malats, Margaret R. Karagas, Paolo Vineis, I-Shou Chang, Dongxin Lin, Baosen Zhou, Adeline Seow, Keitaro Matsuo, Yun-Chul Hong, Neil E. Caporaso, Brian Wolpin, Eric Jacobs, Gloria M. Petersen, Alison P. Klein, Donghui Li, Harvey Risch, Alan R. Sanders, Li Hsu, Robert E. Schoen, Hermann Brenner, MGS (Molecular Genetics of Schizophrenia) GWAS Consortium, GECCO (The Genetics and Epidemiology of Colorectal Cancer Consortium), The GAME-ON/TRICL (Transdisciplinary Research in Cancer of the Lung) GWAS Consortium, PRACTICAL (PRostate cancer AssoCiation group To Investigate Cancer Associated aLterations) Consortium, PanScan Consortium, The GAME-ON/ELLIPSE Consortium, Rachael Stolzenberg-Solomon, Pablo Gejman, Qing Lan, Nathaniel Rothman, Laufey T. Amundadottir, Maria Teresa Landi, Douglas F. Levinson, Stephen J. Chanock, Nilanjan Chatterjee

PLOS Genetics: published December 30, 2016 | https://doi.org/10.1371/journal.pgen.1006493

Dual Roles for Membrane Association of Drosophila Axin in Wnt Signaling

Zhenghan Wang, Ofelia Tacchelly-Benites, Eungi Yang, Yashi Ahmed

PLOS Genetics: published December 13, 2016 | https://doi.org/10.1371/journal.pgen.1006494

NUCLEAR FACTOR Y, Subunit A (NF-YA) Proteins Positively Regulate Flowering and Act Through FLOWERING LOCUS T

Chamindika L. Siriwardana, Nerina Gnesutta, Roderick W. Kumimoto, Daniel S. Jones, Zachary A. Myers, Roberto Mantovani, Ben F. Holt III

PLOS Genetics: published December 15, 2016 | https://doi.org/10.1371/journal.pgen.1006496

Cell Cycle Constraints and Environmental Control of Local DNA Hypomethylation in α-Proteobacteria

Silvia Ardissone, Peter Redder, Giancarlo Russo, Antonio Frandi, Coralie Fumeaux, Andrea Patrignani, Ralph Schlapbach, Laurent Falquet, Patrick H. Viollier

PLOS Genetics: published December 20, 2016 | https://doi.org/10.1371/journal.pgen.1006499

Enrichment of Targetable Mutations in the Relapsed Neuroblastoma Genome

Olivia M. Padovan-Merhar, Pichai Raman, Irina Ostrovnaya, Karthik Kalletla, Kaitlyn R. Rubnitz, Eric M. Sanford, Siraj M. Ali, Vincent A. Miller, Yael P. Mossé, Meaghan P. Granger, Brian Weiss, John M. Maris, Shakeel Modak

PLOS Genetics: published December 20, 2016 | https://doi.org/10.1371/journal.pgen.1006501

Mitochondria and Caspases Tune Nmnat-Mediated Stabilization to Promote Axon Regeneration

Li Chen, Derek M. Nye, Michelle C. Stone, Alexis T. Weiner, Kyle W. Gheres, Xin Xiong, Catherine A. Collins, Melissa M. Rolls

PLOS Genetics: published December 6, 2016 | https://doi.org/10.1371/journal.pgen.1006503

Interaction of Prions Causes Heritable Traits in Saccharomyces cerevisiae

Anton A. Nizhnikov, Tatyana A. Ryzhova, Kirill V. Volkov, Sergey P. Zadorsky, Julia V. Sopova, Sergey G. Inge-Vechtomov, Alexey P. Galkin

PLOS Genetics: published December 27, 2016 | https://doi.org/10.1371/journal.pgen.1006504

Somatic Mutation Patterns in Hemizygous Genomic Regions Unveil Purifying Selection during Tumor Evolution

Jimmy Van den Eynden, Swaraj Basu, Erik Larsson

PLOS Genetics: published December 27, 2016 | https://doi.org/10.1371/journal.pgen.1006506

Elevated Fibroblast Growth Factor Signaling Is Critical for the Pathogenesis of the Dwarfism in Evc2/Limbin Mutant Mice

Honghao Zhang, Nobuhiro Kamiya, Takehito Tsuji, Haruko Takeda, Greg Scott, Sudha Rajderkar, Manas K. Ray, Yoshiyuki Mochida, Benjamin Allen, Veronique Lefebvre, Irene H. Hung, David M. Ornitz, Tetsuo Kunieda, Yuji Mishina

PLOS Genetics: published December 27, 2016 | https://doi.org/10.1371/journal.pgen.1006510

Extensive Regulation of Diurnal Transcription and Metabolism by Glucocorticoids

Benjamin D. Weger, Meltem Weger, Benjamin Görling, Andrea Schink, Cédric Gobet, Céline Keime, Gernot Poschet, Bernard Jost, Nils Krone, Rüdiger Hell, Frédéric Gachon, Burkhard Luy, Thomas Dickmeis

PLOS Genetics: published December 12, 2016 | https://doi.org/10.1371/journal.pgen.1006512

Protein Phosphatase 6 Protects Prophase I-Arrested Oocytes by Safeguarding Genomic Integrity

Meng-Wen Hu, Tie-Gang Meng, Zong-Zhe Jiang, Ming-Zhe Dong, Heide Schatten, Xingzhi Xu, Zhen-Bo Wang, Qing-Yuan Sun

PLOS Genetics: published December 8, 2016 | https://doi.org/10.1371/journal.pgen.1006513

Olfactory Sensory Neurons Control Dendritic Complexity of Mitral Cells via Notch Signaling

Yuko Muroyama, Atsushi Baba, Motoo Kitagawa, Tetsuichiro Saito

PLOS Genetics: published December 27, 2016 | https://doi.org/10.1371/journal.pgen.1006514

Intracellular Zn(II) Intoxication Leads to Dysregulation of the PerR Regulon Resulting in Heme Toxicity in Bacillus subtilis

Pete Chandrangsu, John D. Helmann

PLOS Genetics: published December 9, 2016 | https://doi.org/10.1371/journal.pgen.1006515

PERK Is a Haploinsufficient Tumor Suppressor: Gene Dose Determines Tumor-Suppressive Versus Tumor Promoting Properties of PERK in Melanoma

Dariusz Pytel, Yan Gao, Katarzyna Mackiewicz, Yuliya V. Katlinskaya, Kirk A. Staschke, Maria C. G. Paredes, Akihiro Yoshida, Shuo Qie, Gao Zhang, Olga S. Chajewski, Lawrence Wu, Ireneusz Majsterek, Meenhard Herlyn, Serge Y. Fuchs, J. Alan Diehl

PLOS Genetics: published December 15, 2016 | https://doi.org/10.1371/journal.pgen.1006518

Deep Reads

Deep Reads: Favorites from a Few Different Shelves

Bruce A. Hamilton

PLOS Genetics: published December 15, 2016 | https://doi.org/10.1371/journal.pgen.1006476

December 2016

Cover

Ppp6c deletion causes persistent DNA damage in oocytes within primordial follicles.

Editorial

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