Distinct roles of ATM and ATR in the regulation of ARP8 phosphorylation to prevent chromosome translocations

ELife
Jiying SunSatoshi Tashiro

Abstract

Chromosomal translocations are hallmarks of various types of cancers and leukemias. However, the molecular mechanisms of chromosome translocations remain largely unknown. The ataxia-telangiectasia mutated (ATM) protein, a DNA damage signaling regulator, facilitates DNA repair to prevent chromosome abnormalities. Previously, we showed that ATM deficiency led to the 11q23 chromosome translocation, the most frequent chromosome abnormalities in secondary leukemia. Here, we show that ARP8, a subunit of the INO80 chromatin remodeling complex, is phosphorylated after etoposide treatment. The etoposide-induced phosphorylation of ARP8 is regulated by ATM and ATR, and attenuates its interaction with INO80. The ATM-regulated phosphorylation of ARP8 reduces the excessive loading of INO80 and RAD51 onto the breakpoint cluster region. These findings suggest that the phosphorylation of ARP8, regulated by ATM, plays an important role in maintaining the fidelity of DNA repair to prevent the etoposide-induced 11q23 abnormalities.

References

Dec 23, 1999·The Journal of Biological Chemistry·S T KimM B Kastan
May 10, 2000·The Journal of Biological Chemistry·T O'NeillG A Rathbun
May 18, 2000·Journal of the National Cancer Institute·K K Khanna
Jan 31, 2003·Nature·Christopher J Bakkenist, Michael B Kastan
Mar 4, 2003·Nature Reviews. Cancer·Yosef Shiloh
Apr 25, 2003·Experimental and Molecular Pathology·Alexander J R Bishop, Robert H Schiestl
Oct 19, 2005·The Journal of Biological Chemistry·Jingji JinJoan Weliky Conaway
Dec 6, 2005·Nature Cell Biology·Ali JazayeriStephen P Jackson
Dec 17, 2005·The Journal of Clinical Investigation·Shinichiro NakadaShuki Mizutani
Jan 25, 2006·The Journal of Biological Chemistry·Jeremy S Myers, David Cortez
Feb 8, 2006·The Journal of Experimental Medicine·Myriam CuadradoOscar Fernandez-Capetillo
Apr 25, 2007·Advances in Genetics·Ramune RelieneRobert H Schiestl
Jul 3, 2008·Nature Reviews. Molecular Cell Biology·Karlene A Cimprich, David Cortez
Dec 19, 2009·Nucleic Acids Research·Emma BoldersonKum Kum Khanna
Oct 26, 2010·Biochemical and Biophysical Research Communications·Shu-ichiro KashiwabaYasufumi Murakami
Sep 29, 2011·Molecular and Cellular Biology·Anastas GospodinovZdenko Herceg
Dec 29, 2011·Frontiers in Bioscience (Landmark Edition)·Karina B Falbo, Xuetong Shen
Sep 15, 2012·Nucleic Acids Research·Christian B GerholdKarl-Peter Hopfner
Dec 6, 2012·Proceedings of the National Academy of Sciences of the United States of America·Matheshwaran SaravananDale B Wigley
Mar 15, 2013·Nature Reviews. Molecular Cell Biology·Yosef Shiloh, Yael Ziv
Sep 5, 2013·Cold Spring Harbor Perspectives in Biology·Alexandre Maréchal, Lee Zou
Jun 27, 2014·Frontiers in Genetics·Josée Guirouilh-BarbatBernard S Lopez
Jul 14, 2014·Nucleic Acids Research·Ivelina VassilevaBoyka Anachkova
Feb 19, 2015·Genes & Development·Yong XueMichael F Carey
Mar 4, 2015·FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology·Ning-Ang LiuSatoshi Tashiro
Jul 5, 2015·EMBO Reports·Hanan E Alatwi, Jessica A Downs

❮ Previous
Next ❯

Citations

May 24, 2019·Journal of Biochemistry·Lin ShiSatoshi Tashiro

❮ Previous
Next ❯

Datasets Mentioned

BETA
5888
GeneID
6118
GM0637

Methods Mentioned

BETA
Immunoprecipitation
ChIP
PCR
proximity ligation
Co-immunoprecipitation
immunoprecipitation assay
chromosomal aberrations
transfection
transfections
chemical treatment

Software Mentioned

Image J
Metaystems
MetaSystems
MetaCyte

Related Concepts

Related Feeds

Ataxia telangiectasia (MDS)

Ataxia telangiectasia is a rare neurodegenerative diseases caused by defects in the ATM gene, which is involved in DNA damage recognition and repair pathways. Here is the latest research on this autosomal recessive disease.

Ataxia telangiectasia

Ataxia telangiectasia is a rare neurodegenerative diseases caused by defects in the ATM gene, which is involved in DNA damage recognition and repair pathways. Here is the latest research on this autosomal recessive disease.

Related Papers

Biochemical and Biophysical Research Communications
Shu-ichiro KashiwabaYasufumi Murakami
Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology
M L Bernstein
© 2022 Meta ULC. All rights reserved