This Article
Right arrow Full Text
Right arrow Full Text (PDF)
Right arrow Supplemental material
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Services
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Right arrowReprints and Permissions
Right arrow Copyright Information
Right arrow Books from ASM Press
Right arrow MicrobeWorld
Citing Articles
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Wu, J.
Right arrow Articles by Yu, X.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Wu, J.
Right arrow Articles by Yu, X.

 Previous Article  |  Next Article 

Molecular and Cellular Biology, February 2009, p. 849-860, Vol. 29, No. 3
0270-7306/09/$08.00+0     doi:10.1128/MCB.01302-08
Copyright © 2009, American Society for Microbiology. All Rights Reserved.

Histone Ubiquitination Associates with BRCA1-Dependent DNA Damage Response{triangledown} ,{dagger}

Jiaxue Wu,1 Michael S. Y. Huen,2 Lin-Yu Lu,1 Lin Ye,1 Yali Dou,3 Mats Ljungman,4 Junjie Chen,2 and Xiaochun Yu1*

Division of Molecular Medicine and Genetics, Department of Internal Medicine, University of Michigan Medical School, 109 Zina Pitcher Place, BSRB 1520, Ann Arbor, Michigan 48109,1 Department of Therapeutic Radiology, Yale University School of Medicine, P.O. Box 208040, New Haven, Connecticut 06520,2 Department of Pathology, University of Michigan Medical School, Ann Arbor, Michigan 48109,3 Department of Radiation Oncology, University of Michigan Medical School, Ann Arbor, Michigan 481094

Received 15 August 2008/ Returned for modification 4 September 2008/ Accepted 6 November 2008

Histone ubiquitination participates in multiple cellular processes, including the DNA damage response. However, the molecular mechanisms involved are not clear. Here, we have identified that RAP80/UIMC1 (ubiquitin interaction motif containing 1), a functional partner of BRCA1, recognizes ubiquitinated histones H2A and H2B. The interaction between RAP80 and ubiquitinated histones H2A and H2B is increased following DNA damage. Since RAP80 facilitates BRCA1's translocation to DNA damage sites, our results indicate that ubiquitinated histones H2A and H2B could be upstream partners of the BRCA1/RAP80 complex in the DNA damage response. Moreover, we have found that RNF8 (ring finger protein 8), an E3 ubiquitin ligase, regulates ubiquitination of both histones H2A and H2B. In RNF8-deficient mouse embryo fibroblasts, ubiquitination of both histones H2A and H2B is dramatically reduced, which abolishes the DNA damage-induced BRCA1 and RAP80 accumulation at damage lesions on the chromatin. Taken together, our results suggest that ubiquitinated histones H2A and H2B may recruit the BRCA1 complex to DNA damage lesions on the chromatin.

* Corresponding author. Mailing address: Division of Molecular Medicine and Genetics, Department of Internal Medicine, University of Michigan Medical School, 109 Zina Pitcher Place, BSRB 1520, Ann Arbor, MI 48109. Phone: (734) 615-4945. Fax: (734) 647-7950. E-mail: xiayu{at}umich.edu

{triangledown} Published ahead of print on 17 November 2008.

{dagger} Supplemental material for this article may be found at http://mcb.asm.org/.

Molecular and Cellular Biology, February 2009, p. 849-860, Vol. 29, No. 3
0270-7306/09/$08.00+0     doi:10.1128/MCB.01302-08
Copyright © 2009, American Society for Microbiology. All Rights Reserved.





Copyright © 2009 by the American Society for Microbiology.   For an alternate route to Journals.ASM.org, visit: http://intl-journals.asm.org | More Info»