Biomaterial Database

Increased sensitivity to killing by restriction enzymes in the XR-1 DNA double-strand break repair-deficient mutant. 1990

A J Giaccia, and R A MacLaren, and N Denko, and D Nicolaou, and T D Stamato

Wistar Institute of Anatomy and Biology, Philadelphia, PA 19104.

Repair or misrepair of DNA double-strand breaks (DSBs) is critical in determining cellular survival after gamma-irradiation. In this report, we focus on the cellular and biochemical consequences of restriction enzyme induced DSBs in wild-type Chinese hamster ovary (CHO) cells and the DNA DSB repair-defective mutant XR-1. We find that XR-1 possesses reduced cellular survival after the introduction of restriction enzymes that produce either cohesive or blunt ends. XR-1's sensitivity to killing by restriction enzymes strongly mimics its response to gamma-rays. Using pulsed field electrophoresis, we find that for each enzyme, similar numbers of DNA DSBs are being introduced in both cell lines. The simplest explanation for the increased sensitivity to restriction enzymes in the mutant is that the biochemical defect in XR-1 is not confined to the repair of ionizing radiation induced ends, but extends to DSBs that possess ligatable 3'-hydroxyl and 5'-phosphate ends as well.

UI	MeSH Term	Description	Entries
D009154	Mutation	Any detectable and heritable change in the genetic material that causes a change in the GENOTYPE and which is transmitted to daughter cells and to succeeding generations.	Mutations
D010957	Plasmids	Extrachromosomal, usually CIRCULAR DNA molecules that are self-replicating and transferable from one organism to another. They are found in a variety of bacterial, archaeal, fungal, algal, and plant species. They are used in GENETIC ENGINEERING as CLONING VECTORS.	Episomes,Episome,Plasmid
D002460	Cell Line	Established cell cultures that have the potential to propagate indefinitely.	Cell Lines,Line, Cell,Lines, Cell
D002470	Cell Survival	The span of viability of a cell characterized by the capacity to perform certain functions such as metabolism, growth, reproduction, some form of responsiveness, and adaptability.	Cell Viability,Cell Viabilities,Survival, Cell,Viabilities, Cell,Viability, Cell
D002869	Chromosome Aberrations	Abnormal number or structure of chromosomes. Chromosome aberrations may result in CHROMOSOME DISORDERS.	Autosome Abnormalities,Cytogenetic Aberrations,Abnormalities, Autosome,Abnormalities, Chromosomal,Abnormalities, Chromosome,Chromosomal Aberrations,Chromosome Abnormalities,Cytogenetic Abnormalities,Aberration, Chromosomal,Aberration, Chromosome,Aberration, Cytogenetic,Aberrations, Chromosomal,Aberrations, Chromosome,Aberrations, Cytogenetic,Abnormalities, Cytogenetic,Abnormality, Autosome,Abnormality, Chromosomal,Abnormality, Chromosome,Abnormality, Cytogenetic,Autosome Abnormality,Chromosomal Aberration,Chromosomal Abnormalities,Chromosomal Abnormality,Chromosome Aberration,Chromosome Abnormality,Cytogenetic Aberration,Cytogenetic Abnormality
D004249	DNA Damage	Injuries to DNA that introduce deviations from its normal, intact structure and which may, if left unrepaired, result in a MUTATION or a block of DNA REPLICATION. These deviations may be caused by physical or chemical agents and occur by natural or unnatural, introduced circumstances. They include the introduction of illegitimate bases during replication or by deamination or other modification of bases; the loss of a base from the DNA backbone leaving an abasic site; single-strand breaks; double strand breaks; and intrastrand (PYRIMIDINE DIMERS) or interstrand crosslinking. Damage can often be repaired (DNA REPAIR). If the damage is extensive, it can induce APOPTOSIS.	DNA Injury,DNA Lesion,DNA Lesions,Genotoxic Stress,Stress, Genotoxic,Injury, DNA,DNA Injuries
D004260	DNA Repair	The removal of DNA LESIONS and/or restoration of intact DNA strands without BASE PAIR MISMATCHES, intrastrand or interstrand crosslinks, or discontinuities in the DNA sugar-phosphate backbones.	DNA Damage Response
D004262	DNA Restriction Enzymes	Enzymes that are part of the restriction-modification systems. They catalyze the endonucleolytic cleavage of DNA sequences which lack the species-specific methylation pattern in the host cell's DNA. Cleavage yields random or specific double-stranded fragments with terminal 5'-phosphates. The function of restriction enzymes is to destroy any foreign DNA that invades the host cell. Most have been studied in bacterial systems, but a few have been found in eukaryotic organisms. They are also used as tools for the systematic dissection and mapping of chromosomes, in the determination of base sequences of DNAs, and have made it possible to splice and recombine genes from one organism into the genome of another. EC 3.21.1.	Restriction Endonucleases,DNA Restriction Enzyme,Restriction Endonuclease,Endonuclease, Restriction,Endonucleases, Restriction,Enzymes, DNA Restriction,Restriction Enzyme, DNA,Restriction Enzymes, DNA
D005954	Glucosephosphate Dehydrogenase		Glucose-6-Phosphate Dehydrogenase,Dehydrogenase, Glucose-6-Phosphate,Dehydrogenase, Glucosephosphate,Glucose 6 Phosphate Dehydrogenase
D006064	Gonadotropins, Equine	Gonadotropins secreted by the pituitary or the placenta in horses. This term generally refers to the gonadotropins found in the pregnant mare serum, a rich source of equine CHORIONIC GONADOTROPIN; LUTEINIZING HORMONE; and FOLLICLE STIMULATING HORMONE. Unlike that in humans, the equine LUTEINIZING HORMONE, BETA SUBUNIT is identical to the equine choronic gonadotropin, beta. Equine gonadotropins prepared from pregnant mare serum are used in reproductive studies.	Pregnant Mare Serum Gonadotropins,PMS Gonadotropins,PMSG (Gonadotropins),Equine Gonadotropins,Gonadotropins, PMS