DNA cross-link repair safeguards genomic stability during premeiotic germ cell development

Nature Genetics
Ross J Hill, Gerry P Crossan

Abstract

Germline de novo mutations are the basis of evolutionary diversity but also of genetic disease. However, the molecular origin, mechanisms and timing of germline mutagenesis are not fully understood. Here, we define a fundamental role for DNA interstrand cross-link repair in the germline. This repair process is essential for primordial germ cell (PGC) maturation during embryonic development. Inactivation of cross-link repair leads to genetic instability that is restricted to PGCs within the genital ridge during a narrow temporal window. Having successfully activated the PGC transcriptional program, a potent quality control mechanism detects and drives damaged PGCs into apoptosis. Therefore, these findings define a source of DNA damage and the nature of the subsequent DNA repair response in germ cells, which ensures faithful transmission of the genome between generations.

References

May 1, 1988·Journal of the American Academy of Dermatology·P G NorrisF Giannelli
Feb 1, 1997·Chromosome Research : an International Journal on the Molecular, Supramolecular and Evolutionary Aspects of Chromosome Biology·A H PetersP de Boer
Nov 14, 1997·Nature Genetics·A Olek, J Walter
Jun 7, 2002·Mechanisms of Development·Piroska E SzabóJeffrey R Mann
Sep 3, 2002·Mechanisms of Development·Petra HajkovaM Azim Surani
Aug 2, 2003·Genes & Development·Scott HoughtalingMarkus Grompe
May 25, 2004·Nature Genetics·F William BuaasRobert E Braun
Jun 7, 2005·Nature·Yasuhide OhinataM Azim Surani
Nov 18, 2005·Development·Yutaka TakeuchiChris Wylie
Jan 27, 2006·Genesis : the Journal of Genetics and Development·Bernhard PayerM Azim Surani
Dec 22, 2006·Nature·Laura J NiedernhoferJan H J Hoeijmakers
Jun 11, 2008·Molecular and Cellular Biology·Anwaar AhmadLaura J Niedernhofer
Nov 22, 2008·Cold Spring Harbor Symposia on Quantitative Biology·M A SuraniW W Tee
Jul 23, 2009·Mutation Research·Arleen D Auerbach
Jul 8, 2011·Nature·Frédéric LangevinKetan J Patel
Nov 15, 2011·Nature Structural & Molecular Biology·Ivan V RosadoKetan J Patel
Mar 1, 2012·Blood·Lars U W MüllerDavid A Williams
Apr 10, 2012·Cell Stem Cell·Astrid GillichM Azim Surani
May 23, 2012·Cell·Serena Nik-ZainalUNKNOWN Breast Cancer Working Group of the International Cancer Genome Consortium
May 23, 2012·Blood·Juan P TrujilloJordi Surrallés
Jul 19, 2012·Nature Reviews. Genetics·Joris A Veltman, Han G Brunner
Dec 12, 2012·Molecular Cell·Stefanie SeisenbergerWolf Reik
Jan 16, 2013·Cell Reports·Ludmil B AlexandrovMichael R Stratton
Jan 18, 2013·Nature·Molly C Kottemann, Agata Smogorzewska

❮ Previous
Next ❯

Citations

Oct 20, 2019·Theory in Biosciences = Theorie in Den Biowissenschaften·Donald R Forsdyke
Jan 28, 2021·Seminars in Cell & Developmental Biology·Vallari ShuklaEva R Hoffmann
Nov 14, 2020·Genes & Development·Jordana C Bloom, John C Schimenti
Feb 10, 2021·Seminars in Cell & Developmental Biology·Laure Guitton-SertJean-Yves Masson

❮ Previous
Next ❯

Methods Mentioned

BETA
flow cytometry
PCR
electrophoresis
transgenic
genotyping
fluorescence imaging
FCS
FACS

Software Mentioned

QUantification tool for Methylation Analysis ( QUMA )
FlowJo
CometScore

Related Concepts

Related Feeds

Apoptosis

Apoptosis is a specific process that leads to programmed cell death through the activation of an evolutionary conserved intracellular pathway leading to pathognomic cellular changes distinct from cellular necrosis

Related Papers

Current Topics in Developmental Biology
Daniel H NguyenDiana J Laird
Seikagaku. The Journal of Japanese Biochemical Society
Masamichi Ishiai
Proceedings of the National Academy of Sciences of the United States of America
Yohei HayashiYasuhisa Matsui
Cold Spring Harbor Perspectives in Biology
Mitinori Saitou, Masashi Yamaji
Current Topics in Developmental Biology
Harry G LeitchM Azim Surani
© 2021 Meta ULC. All rights reserved