QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

Vol. 16, Issue 10, 5013-5025, October 2005

This Article Full Text Full Text (PDF) Supplemental Material All Versions of this Article: E05-01-0065v1 16/10/5013    most recent Alert me when this article is cited Alert me if a correction is posted Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by McManus, K. J. Articles by Hendzel, M. J. Search for Related Content PubMed PubMed Citation Articles by McManus, K. J. Articles by Hendzel, M. J.

ATM-dependent DNA Damage-independent Mitotic Phosphorylation of H2AX in Normally Growing Mammalian Cells

Department of Oncology, University of Alberta, Cross Cancer Institute, Edmonton, Alberta T6G 1Z2, Canada

Submitted January 24, 2005; Revised June 13, 2005; Accepted July 8, 2005
Monitoring Editor: Kerry Bloom

H2AX is a core histone H2A variant that contains an absolutely conserved serine/glutamine (SQ) motif within an extended carboxy-terminal tail. H2AX phosphorylation at the SQ motif (-H2AX) has been shown to increase dramatically upon exogenously introduced DNA double-strand breaks (DSBs). In this study, we use quantitative in situ approaches to investigate the spatial patterning and cell cycle dynamics of -H2AX in a panel of normally growing (unirradiated) mammalian cell lines and cultures. We provide the first evidence for the existence of two distinct yet highly discernible -H2AX focal populations: a small population of large amorphous foci that colocalize with numerous DNA DSB repair proteins and previously undescribed but much more abundant small foci. These small foci do not recruit proteins involved in DNA DSB repair. Cell cycle analyses reveal unexpected dynamics for -H2AX in unirradiated mammalian cells that include an ATM-dependent phosphorylation that is maximal during M phase. Based upon similarities drawn from other histone posttranslational modifications and previous observations in haploinsufficient (H2AX^-/+) and null mice (H2AX^-/-), -H2AX may contribute to the fidelity of the mitotic process, even in the absence of DNA damage, thereby ensuring the faithful transmission of genetic information from one generation to the next.

Abbreviations used: ATM, ataxia telangiectasia mutated; DNA DSB, DNA double-strand break; DIM, digital imaging microscopy; DNA-PK_CS, DNA protein kinase, catalytic subunit; M, metaphase; P/PM, prophase/prometaphase; QIM, quantitative imaging microscopy.

The online version of this article contains supplemental material at MBC Online (http://www.molbiolcell.org).

Address correspondence to: Michael J. Hendzel (michaelh{at}cancerboard.ab.ca).

This article has been cited by other articles:

				A. Derijck, G. van der Heijden, M. Giele, M. Philippens, and P. de Boer DNA double-strand break repair in parental chromatin of mouse zygotes, the first cell cycle as an origin of de novo mutation Hum. Mol. Genet., July 1, 2008; 17(13): 1922 - 1937. [Abstract] [Full Text] [PDF]

				S. L. Bailey, K. E. Gurley, K. Hoon-Kim, K. S. Kelly-Spratt, and C. J. Kemp Tumor Suppression by p53 in the Absence of Atm Mol. Cancer Res., July 1, 2008; 6(7): 1185 - 1192. [Abstract] [Full Text] [PDF]

				A. Hadnagy, R. Beaulieu, and D. Balicki Histone tail modifications and noncanonical functions of histones: perspectives in cancer epigenetics Mol. Cancer Ther., April 1, 2008; 7(4): 740 - 748. [Abstract] [Full Text] [PDF]

				F. Leduc, V. Maquennehan, G. B. Nkoma, and G. Boissonneault DNA Damage Response During Chromatin Remodeling in Elongating Spermatids of Mice Biol Reprod, February 1, 2008; 78(2): 324 - 332. [Abstract] [Full Text] [PDF]

				T. S. Barton, B. Robaire, and B. F. Hales DNA Damage Recognition in the Rat Zygote Following Chronic Paternal Cyclophosphamide Exposure Toxicol. Sci., December 1, 2007; 100(2): 495 - 503. [Abstract] [Full Text] [PDF]

				S. C. Pruitt, K. J. Bailey, and A. Freeland Reduced Mcm2 Expression Results in Severe Stem/Progenitor Cell Deficiency and Cancer Stem Cells, December 1, 2007; 25(12): 3121 - 3132. [Abstract] [Full Text] [PDF]

				S. Hanasoge and M. Ljungman H2AX phosphorylation after UV irradiation is triggered by DNA repair intermediates and is mediated by the ATR kinase Carcinogenesis, November 1, 2007; 28(11): 2298 - 2304. [Abstract] [Full Text] [PDF]

				A. A.H.A. Derijck, G. W. van der Heijden, L. Ramos, M. Giele, J. A.M. Kremer, and P. de Boer Motile human normozoospermic and oligozoospermic semen samples show a difference in double-strand DNA break incidence Hum. Reprod., September 1, 2007; 22(9): 2368 - 2376. [Abstract] [Full Text] [PDF]

				M. J. Cariveau, X. Tang, X.-L. Cui, and B. Xu Characterization of an NBS1 C-Terminal Peptide That Can Inhibit Ataxia Telangiectasia Mutated (ATM)-Mediated DNA Damage Responses and Enhance Radiosensitivity Mol. Pharmacol., August 1, 2007; 72(2): 320 - 326. [Abstract] [Full Text] [PDF]

				V. A. Rao, C. Conti, J. Guirouilh-Barbat, A. Nakamura, Z.-H. Miao, S. L. Davies, B. Sacca, I. D. Hickson, A. Bensimon, and Y. Pommier Endogenous {gamma}-H2AX-ATM-Chk2 Checkpoint Activation in Bloom's Syndrome Helicase Deficient Cells Is Related to DNA Replication Arrested Forks Mol. Cancer Res., July 1, 2007; 5(7): 713 - 724. [Abstract] [Full Text] [PDF]

				A. Shiras, S. T Chettiar, V. Shepal, G. Rajendran, G. R. Prasad, and P. Shastry Spontaneous Transformation of Human Adult Nontumorigenic Stem Cells to Cancer Stem Cells Is Driven by Genomic Instability in a Human Model of Glioblastoma Stem Cells, June 1, 2007; 25(6): 1478 - 1489. [Abstract] [Full Text] [PDF]

				B. Eymin, P. Claverie, C. Salon, C. Leduc, E. Col, E. Brambilla, S. Khochbin, and S. Gazzeri p14ARF Activates a Tip60-Dependent and p53-Independent ATM/ATR/CHK Pathway in Response to Genotoxic Stress. Mol. Cell. Biol., June 1, 2006; 26(11): 4339 - 4350. [Abstract] [Full Text] [PDF]