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PMID: 11934988 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't Research Support, U.S. Gov't, P.H.S.

Genomic instability in mice lacking histone H2AX.

Science (New York, N.Y.) ·Vol. 296 ·No. 5569 ·2002-05-03 ·Pages 922-7

Celeste A, Petersen S, Romanienko PJ, Fernandez-Capetillo O, Chen HT, Sedelnikova OA, Reina-San-Martin B, Coppola V, Meffre E, Difilippantonio MJ, Redon C, Pilch DR, Olaru A, Eckhaus M, Camerini-Otero RD, Tessarollo L, Livak F, Manova K, Bonner WM, Nussenzweig MC, Nussenzweig A

Abstract

Higher order chromatin structure presents a barrier to the recognition and repair of DNA damage. Double-strand breaks (DSBs) induce histone H2AX phosphorylation, which is associated with the recruitment of repair factors to damaged DNA. To help clarify the physiological role of H2AX, we targeted H2AX in mice. Although H2AX is not essential for irradiation-induced cell-cycle checkpoints, H2AX-/- mice were radiation sensitive, growth retarded, and immune deficient, and mutant males were infertile. These pleiotropic phenotypes were associated with chromosomal instability, repair defects, and impaired recruitment of Nbs1, 53bp1, and Brca1, but not Rad51, to irradiation-induced foci. Thus, H2AX is critical for facilitating the assembly of specific DNA-repair complexes on damaged DNA.

MeSH Terms
Amino Acid Sequence Animals B-Lymphocytes/immunology,physiology Base Sequence Cell Cycle Cells, Cultured Cellular Senescence Chromosome Aberrations DNA Damage DNA Repair Female Gene Targeting Histones/chemistry,genetics,physiology Immunoglobulin Class Switching Infertility, Male/genetics,physiopathology Lymphocyte Count Male Meiosis Mice Mice, Knockout Molecular Sequence Data Mutation Phosphorylation Recombination, Genetic Spermatocytes/physiology T-Lymphocytes/immunology,physiology
Chemicals
Histones
Authors & Affiliations
21 authors, click to expand affiliations / ORCID
Celeste Arkady
Experimental Immunology Branch, National Cancer Institute, NIH, Bethesda, MD 20892, USA.
Petersen Simone
Romanienko Peter J
Fernandez-Capetillo Oscar
Chen Hua Tang
Sedelnikova Olga A
Reina-San-Martin Bernardo
Coppola Vincenzo
Meffre Eric
Difilippantonio Michael J
Redon Christophe
Pilch Duane R
Olaru Alexandru
Eckhaus Michael
Camerini-Otero R Daniel
Tessarollo Lino
Livak Ferenc
Manova Katia
Bonner William M
Nussenzweig Michel C
Nussenzweig André
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Article Info
Journal
Science (New York, N.Y.)
Abbr.
Science
ISSN
1095-9203
DOI
10.1126/science.1069398
Published
2002-05-03
Epub
2002-00-04
Pages
922-7
Language
English
Region
United States
NLM ID
0404511
PMCID
PMC4721576
Subset
IM
Grants
Intramural NIH HHS · Z99 CA999999 · United States
External Links
PubMed source DOI: 10.1126/science.1069398 PMC Full Text View journal details
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