Nuclear lamina dysfunction triggers a germline stem cell checkpoint

Lacy J Barton; Tingting Duan; Wenfan Ke; Amy Luttinger; Kaylee E Lovander; Alexey A Soshnev; Pamela K Geyer

doi:10.1038/s41467-018-06277-z

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Nuclear lamina dysfunction triggers a germline stem cell checkpoint

Journal article

Open access

Peer reviewed

Nuclear lamina dysfunction triggers a germline stem cell checkpoint

Lacy J Barton, Tingting Duan, Wenfan Ke, Amy Luttinger, Kaylee E Lovander, Alexey A Soshnev and Pamela K Geyer

Nature communications, Vol.9(1), pp.3960-13

09/27/2018

DOI: 10.1038/s41467-018-06277-z

PMCID: PMC6160405

PMID: 30262885

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Abstract

LEM domain (LEM-D) proteins are conserved components of the nuclear lamina (NL) that contribute to stem cell maintenance through poorly understood mechanisms. The Drosophila emerin homolog Otefin (Ote) is required for maintenance of germline stem cells (GSCs) and gametogenesis. Here, we show that ote mutants carry germ cell-specific changes in nuclear architecture that are linked to GSC loss. Strikingly, we found that both GSC death and gametogenesis are rescued by inactivation of the DNA damage response (DDR) kinases, ATR and Chk2. Whereas the germline checkpoint draws from components of the DDR pathway, genetic and cytological features of the GSC checkpoint differ from the canonical pathway. Instead, structural deformation of the NL correlates with checkpoint activation. Despite remarkably normal oogenesis, rescued oocytes do not support embryogenesis. Taken together, these data suggest that NL dysfunction caused by Otefin loss triggers a GSC-specific checkpoint that contributes to maintenance of gamete quality.

Animals

Cell Cycle Checkpoints

Checkpoint Kinase 2 - metabolism

DNA Damage

DNA Transposable Elements - genetics

Drosophila melanogaster - cytology

Drosophila melanogaster - metabolism

Drosophila Proteins - metabolism

Female

Germ Cells - metabolism

Male

Membrane Proteins

Models, Biological

Mutation - genetics

Nuclear Lamina - metabolism

Nuclear Proteins

Oogenesis

Stem Cells - cytology

Stem Cells - metabolism

Transcription, Genetic

Details

Title: Subtitle: Nuclear lamina dysfunction triggers a germline stem cell checkpoint
Creators: Lacy J Barton - University of Iowa
Tingting Duan - University of Iowa
Wenfan Ke - University of Iowa
Amy Luttinger - University of Iowa
Kaylee E Lovander - University of Iowa
Alexey A Soshnev - University of Iowa
Pamela K Geyer - University of Iowa
Resource Type: Journal article
Publication Details: Nature communications, Vol.9(1), pp.3960-13
DOI: 10.1038/s41467-018-06277-z
PMID: 30262885
PMCID: PMC6160405
NLM abbreviation: Nat Commun
ISSN: 2041-1723
eISSN: 2041-1723
Grant note: DRG-2185-14 / Damon Runyon Cancer Research Foundation (Damon Runyon) R01 GM087341 / NIGMS NIH HHS GM087341 / U.S. Department of Health & Human Services | NIH | National Institute of General Medical Sciences (NIGMS) S10 RR025439 / NCRR NIH HHS
Language: English
Date published: 09/27/2018
Academic Unit: Obstetrics and Gynecology; Biochemistry and Molecular Biology
Record Identifier: 9984293076602771

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