Histone H1 functions as a stimulatory factor in backup pathways of NHEJ

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 l...

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Bibliographic Details
Published in:Nucleic acids research 2008-03, Vol.36 (5), p.1610-1623
Main Authors: Rosidi, Bustanur, Wang, Minli, Wu, Wenqi, Sharma, Aparna, Wang, Huichen, Iliakis, George
Format: Article
Language:English
Subjects:
Cell Extracts - chemistry
Cell Nucleus - chemistry
DNA - chemistry
DNA - metabolism
DNA Breaks, Double-Stranded
DNA Ligases - metabolism
DNA Repair
HeLa Cells
Histones - chemistry
Histones - isolation & purification
Histones - metabolism
Humans
Molecular Biology
Poly (ADP-Ribose) Polymerase-1
Poly(ADP-ribose) Polymerases - metabolism
Tandem Mass Spectrometry
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Summary: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.
ISSN:0305-1048
1362-4962
DOI:10.1093/nar/gkn013