Eya2 promotes cell cycle progression by regulating DNA damage response during vertebrate limb regeneration.

ELife
Konstantinos SousounisJessica L Whited

Abstract

How salamanders accomplish progenitor cell proliferation while faithfully maintaining genomic integrity and regenerative potential remains elusive. Here we found an innate DNA damage response mechanism that is evident during blastema proliferation (early- to late-bud) and studied its role during tissue regeneration by ablating the function of one of its components, Eyes absent 2. In eya2 mutant axolotls, we found that DNA damage signaling through the H2AX histone variant was deregulated, especially within the proliferating progenitors during limb regeneration. Ultimately, cell cycle progression was impaired at the G1/S and G2/M transitions and regeneration rate was reduced. Similar data were acquired using acute pharmacological inhibition of the Eya2 phosphatase activity and the DNA damage checkpoint kinases Chk1 and Chk2 in wild-type axolotls. Together, our data indicate that highly-regenerative animals employ a robust DNA damage response pathway which involves regulation of H2AX phosphorylation via Eya2 to facilitate proper cell cycle progression upon injury.

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Citations

Jul 31, 2020·Critical Reviews in Biochemistry and Molecular Biology·Rashmi S HegdeRam Naresh Pandey
Dec 10, 2020·Developmental Dynamics : an Official Publication of the American Association of Anatomists·Ulises Omar García-LepeRosa María Bermúdez-Cruz
Mar 15, 2021·Developmental Dynamics : an Official Publication of the American Association of Anatomists·Ting ZhangPin-Xian Xu
May 6, 2021·Developmental Dynamics : an Official Publication of the American Association of Anatomists·Lydia TilleyPrayag Murawala
Jun 25, 2021·Frontiers in Cell and Developmental Biology·Maximina H Yun
Oct 5, 2021·Annals of the New York Academy of Sciences·Jennifer CableMerrit Romeike

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Datasets Mentioned

BETA
PRJNA573629

Methods Mentioned

BETA
RNAseq
electrophoresis
amputation
immunoprecipitation
RNA-seq
Co-immunoprecipitation
genotyping
amputations
dissecting
X-ray

Software Mentioned

RNAseq
Swiss
ClustalW
PdbViewer
Axolotl
Evos
Adobe Photoshop
ImageJ
STRING
ZiFiT

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