Year: 2011
Type: article
Abstract: Uracil is removed from DNA by the conserved enzyme uracil DNA N-glycosylase (UNG). Previously, we observed that inhibiting UNG in Xenopus egg extracts blocked assembly of CENP-A, a histone H3 variant. CENP-A is an essential protein in all species, since it is required for chromosome segregation during mitosis. Thus, the implication of UNG in CENP-A assembly implies that UNG would also be essential, but UNG mutants lacking catalytic activity are viable in all species. In this paper, we present evidence that UNG2 colocalizes with CENP-A and H2AX phosphorylation at centromeres in normally cycling cells. Reduction of UNG2 in human cells blocks CENP-A assembly, and results in reduced cell proliferation, associated with increased frequencies of mitotic abnormalities and rapid cell death. Overexpression of UNG2 induces high levels of CENP-A assembly in human cells. Using a multiphoton laser approach, we demonstrate that UNG2 is rapidly recruited to sites of DNA damage. Taken together, our data are consistent with a model in which the N-terminus of UNG2 interacts with the active site of the enzyme and with chromatin.
Source: PLoS ONE
Language: English
Topic: DNA Repair Mechanisms
Subfield: Molecular Biology
Domain: Life Sciences
Open Access status: gold
Estimated APC paid: $2,382
Funders: California Institute of Regenerative Medicine, Ludwig Institute for Cancer Research, Norges Forskningsråd, St. Olavs Hospital Universitetssykehuset i Trondheim, National Institutes of Health, University of California, San Diego, National Cancer Institute, National Institute of General Medical Sciences, National Institute of Neurological Disorders and Stroke
Awards: G2055182882, G3033040839, Biochemical Basis of CENP-A Epigenetic Inheritance, G3185024015, G3564244690, Biological Function of the Retinoblastoma Gene Product, G5690587020, University of California San Diego Neuroscience Microscopy Imaging Core, G639426234, Nuclear Function of the c-Abl Protooncoprotien, Specialized Cancer Center Support Grant, G8770478079, Nuclear Function of Abl in DNA Damage Response, G9000064842, G9000255603
OpenAlex ID: W2110694293