Genomic instability in mice lacking histone H2AX

被引：1142

作者：

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 ^{[1
]}

机构：

[1] NCI, Expt Immunol Branch, NIH, Bethesda, MD 20892 USA

[2] NIDDKD, Genet & Biochem Branch, NIH, Bethesda, MD 20892 USA

[3] NIH, Mol Pharmacol Lab, Bethesda, MD 20892 USA

[4] Rockefeller Univ, Howard Hughes Med Inst, Lab Mol Immunol, New York, NY 10021 USA

[5] NIH, Mouse Canc Genet Program, Frederick, MD 20892 USA

[6] NCI, Dept Genet, NIH, Bethesda, MD 20892 USA

[7] Univ Maryland, Sch Med, Dept Microbiol & Immunol, Baltimore, MD 21201 USA

[8] NIH, Vet Resources Program, Natl Ctr Res Resources, Bethesda, MD 20892 USA

[9] Mem Sloan Kettering Canc Ctr, Mol Cytol Core Facil, New York, NY 10021 USA

[10] Mem Sloan Kettering Canc Ctr, Program Mol Biol, New York, NY 10021 USA

来源：

SCIENCE | 2002年 / 296卷 / 5569期

关键词：

D O I：

10.1126/science.1069398

中图分类号：

O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];

学科分类号：

07 [理学]; 0710 [生物学]; 09 [农学];

摘要：

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.

引用

页码：922 / 927

页数：6

共 33 条

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