Nucleic Acids Research Advance Access originally published online on February 3, 2008
Nucleic Acids Research 2008 36(5):1610-1623; doi:10.1093/nar/gkn013
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Nucleic Acids Research, 2008, Vol. 36, No. 5 1610-1623
© 2008 The Author(s)
This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/2.0/uk/) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.
Molecular Biology |
Histone H1 functions as a stimulatory factor in backup pathways of NHEJ
1University of Duisburg-Essen, Medical School, Institute of Medical Radiation Biology, 45122 Essen, Germany and 2Center for Neurovirology, Temple University, Philadelphia, PA 19122, USA
*To whom correspondence should be addressed. Tel: +49 201 723 4152; Fax: +49 201 723 5966; Email: georg.iliakis{at}uk-essen.de
Received December 12, 2007. Revised January 8, 2008. Accepted January 8, 2008.
DNA double-strand breaks (DSBs) induced in the genome of higher eukaryotes by ionizing radiation (IR) are predominantly removed by two pathways of non-homologous end-joining (NHEJ) termed D-NHEJ and B-NHEJ. While D-NHEJ depends on the activities of the DNA-dependent protein kinase (DNA-PK) and DNA ligase IV/XRCC4/XLF, B-NHEJ utilizes, at least partly, DNA ligase III/XRCC1 and PARP-1. Using in vitro end-joining assays and protein fractionation protocols similar to those previously applied for the characterization of DNA ligase III as an end-joining factor, we identify here histone H1 as an additional putative NHEJ factor. H1 strongly enhances DNA-end joining and shifts the product spectrum from circles to multimers. While H1 enhances the DNA-end-joining activities of both DNA Ligase IV and DNA Ligase III, the effect on ligase III is significantly stronger. Histone H1 also enhances the activity of PARP-1. Since histone H1 has been shown to counteract D-NHEJ, these observations and the known functions of the protein identify it as a putative alignment factor operating preferentially within B-NHEJ.
Present address: Wenqi Wu, Department of Urology, Minimally Invasive Surgery Center, The First Affiliated Hospital of Guangzhou Medical College, Guangzhou, P.R.China.
The authors wish it to be known that, in their opinion, the first two authors should be regarded as joint First Authors.