Genomic Instability in Mice Lacking Histone H2AX | Zendy

Arkady Celeste | Zendy; Simone Petersen | Zendy; Peter Romanienko | Zendy; Óscar Fernández-Capetillo | Zendy; Hua Tang Chen | Zendy; Olga A. Sedelnikova | Zendy; Bernardo ReinaSanMartin | Zendy; Vincenzo Coppola | Zendy; Eric Meffre | Zendy; Michael J. Difilippantonio | Zendy; Christophe E. Redon | Zendy; Duane R. Pilch | Zendy; Alexandru Olaru | Zendy; Michael Eckhaus | Zendy; R. Daniel CameriniOtero | Zendy; Lino Tessarollo | Zendy; Ferenc Livák | Zendy; Katia Manova | Zendy; William M. Bonner | Zendy; Michel C. Nussenzweig | Zendy; André Nussenzweig | Zendy

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Genomic Instability in Mice Lacking Histone H2AX

Author(s) -

Arkady Celeste,

Simone Petersen,

Peter Romanienko,

Óscar Fernández-Capetillo,

Hua Tang Chen,

Olga A. Sedelnikova,

Bernardo ReinaSanMartin,

Vincenzo Coppola,

Eric Meffre,

Michael J. Difilippantonio,

Christophe E. Redon,

Duane R. Pilch,

Alexandru Olaru,

Michael Eckhaus,

R. Daniel CameriniOtero,

Lino Tessarollo,

Ferenc Livák,

Katia Manova,

William M. Bonner,

Michel C. Nussenzweig,

André Nussenzweig

Publication year - 2002

Publication title -

science

Language(s) - Uncategorized

Resource type - Journals

SCImago Journal Rank - 12.556

H-Index - 1186

eISSN - 1095-9203

pISSN - 0036-8075

DOI - 10.1126/science.1069398

Subject(s) - genome instability , rad51 , dna damage , dna repair , chromatin , histone , biology , microbiology and biotechnology , dna , chromosome instability , homologous recombination , mutant , genetics , cancer research , gene , chromosome

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.

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