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Focus on Histone Variant H2AX: to Be or Not to Be

Overview
Journal FEBS Lett
Specialty Biochemistry
Date 2010 May 25
PMID 20493860
Citations 135
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Abstract

Phosphorylation of histone variant H2AX at serine 139, named gammaH2AX, has been widely used as a sensitive marker for DNA double-strand breaks (DSBs). gammaH2AX is required for the accumulation of many DNA damage response (DDR) proteins at DSBs. Thus it is believed to be the principal signaling protein involved in DDR and to play an important role in DNA repair. However, only mild defects in DNA damage signaling and DNA repair were observed in H2AX-deficient cells and animals. Such findings prompted us and others to explore H2AX-independent mechanisms in DNA damage response. Here, we will review recent advances in our understanding of H2AX-dependent and independent DNA damage signaling and repair pathways in mammalian cells.

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References
1.
Reina-San-Martin B, Difilippantonio S, Hanitsch L, Masilamani R, Nussenzweig A, Nussenzweig M . H2AX is required for recombination between immunoglobulin switch regions but not for intra-switch region recombination or somatic hypermutation. J Exp Med. 2003; 197(12):1767-78. PMC: 2193951. DOI: 10.1084/jem.20030569. View

2.
Xu Y, Ashley T, Brainerd E, Bronson R, Meyn M, Baltimore D . Targeted disruption of ATM leads to growth retardation, chromosomal fragmentation during meiosis, immune defects, and thymic lymphoma. Genes Dev. 1996; 10(19):2411-22. DOI: 10.1101/gad.10.19.2411. View

3.
Kim H, Chen J, Yu X . Ubiquitin-binding protein RAP80 mediates BRCA1-dependent DNA damage response. Science. 2007; 316(5828):1202-5. DOI: 10.1126/science.1139621. View

4.
Doil C, Mailand N, Bekker-Jensen S, Menard P, Larsen D, Pepperkok R . RNF168 binds and amplifies ubiquitin conjugates on damaged chromosomes to allow accumulation of repair proteins. Cell. 2009; 136(3):435-46. DOI: 10.1016/j.cell.2008.12.041. View

5.
Mukherjee B, Kessinger C, Kobayashi J, Chen B, Chen D, Chatterjee A . DNA-PK phosphorylates histone H2AX during apoptotic DNA fragmentation in mammalian cells. DNA Repair (Amst). 2006; 5(5):575-90. DOI: 10.1016/j.dnarep.2006.01.011. View