Linked Life Data

18157161

Source:http://linkedlifedata.com/resource/pubmed/id/18157161

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
1
pubmed:dateCreated
2008-1-7
pubmed:abstractText
DNA double-strand breaks (DSBs) are critical lesions that can result in cell death or a wide variety of genetic alterations including large- or small-scale deletions, loss of heterozygosity, translocations, and chromosome loss. DSBs are repaired by non-homologous end-joining (NHEJ) and homologous recombination (HR), and defects in these pathways cause genome instability and promote tumorigenesis. DSBs arise from endogenous sources including reactive oxygen species generated during cellular metabolism, collapsed replication forks, and nucleases, and from exogenous sources including ionizing radiation and chemicals that directly or indirectly damage DNA and are commonly used in cancer therapy. The DSB repair pathways appear to compete for DSBs, but the balance between them differs widely among species, between different cell types of a single species, and during different cell cycle phases of a single cell type. Here we review the regulatory factors that regulate DSB repair by NHEJ and HR in yeast and higher eukaryotes. These factors include regulated expression and phosphorylation of repair proteins, chromatin modulation of repair factor accessibility, and the availability of homologous repair templates. While most DSB repair proteins appear to function exclusively in NHEJ or HR, a number of proteins influence both pathways, including the MRE11/RAD50/NBS1(XRS2) complex, BRCA1, histone H2AX, PARP-1, RAD18, DNA-dependent protein kinase catalytic subunit (DNA-PKcs), and ATM. DNA-PKcs plays a role in mammalian NHEJ, but it also influences HR through a complex regulatory network that may involve crosstalk with ATM, and the regulation of at least 12 proteins involved in HR that are phosphorylated by DNA-PKcs and/or ATM.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Jan
pubmed:issn
1748-7838
pubmed:author
pubmed:issnType
Electronic
pubmed:volume
18
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
134-47
pubmed:dateRevised
2011-11-2
pubmed:meshHeading
pubmed-meshheading:18157161-Animals, pubmed-meshheading:18157161-Cell Cycle, pubmed-meshheading:18157161-Cell Cycle Proteins, pubmed-meshheading:18157161-Chromosome Aberrations, pubmed-meshheading:18157161-DNA Breaks, Double-Stranded, pubmed-meshheading:18157161-DNA Repair, pubmed-meshheading:18157161-DNA-Activated Protein Kinase, pubmed-meshheading:18157161-DNA-Binding Proteins, pubmed-meshheading:18157161-Eukaryotic Cells, pubmed-meshheading:18157161-Genomic Instability, pubmed-meshheading:18157161-Humans, pubmed-meshheading:18157161-Models, Biological, pubmed-meshheading:18157161-Nuclear Proteins, pubmed-meshheading:18157161-Protein-Serine-Threonine Kinases, pubmed-meshheading:18157161-Recombination, Genetic, pubmed-meshheading:18157161-Signal Transduction, pubmed-meshheading:18157161-Species Specificity, pubmed-meshheading:18157161-Tumor Suppressor Proteins, pubmed-meshheading:18157161-Yeasts
pubmed:year
2008
pubmed:articleTitle
Regulation of DNA double-strand break repair pathway choice.
pubmed:affiliation
Department of Molecular Genetics and Microbiology, University of New Mexico School of Medicine and Cancer Center, Albuquerque, NM 87131, USA.
pubmed:publicationType
Journal Article, Review, Research Support, N.I.H., Extramural