Biomaterial Database

Higher-order chromatin structure-dependent repair of DNA double-strand breaks: modeling the elution of DNA from nucleoids. 1997

P J Johnston, and P L Olive, and P E Bryant

Medical Biophysics Department, British Columbia Cancer Research Centre, Vancouver, Canada.

A possible relationship between the repair of DNA double-strand breaks (DSBs) and their distribution within higher-order chromatin (Johnston and Bryant, Int. J. Radiat. Biol. 66, 531-536, 1994) has recently been demonstrated. Radiosensitive cells deficient for components of the DNA-dependent protein kinase DSB repair pathway exhibited a particular failure in the rejoining of DSBs occurring as multiples within looped DNA structures. Here, a Poisson-based model of induction of DSBs and elution of DNA from residual nuclear structures is presented. By applying this model to cells of a panel of human and rodent cell lines, a mean of 1.6 Mbp for the size of the relevant looped structures was obtained. Such large chromatin structures are of the same magnitude as those observed by functional mapping of interphase and mitotic chromosome structure, nucleoid sedimentation and the "replicon clusters" apparent during DNA replication. This work supports the hypotheses that (1) such structures are critical targets for induction of DSBs and (2) the distribution of damage within these domains may be a factor in the response and sensitivity of mammalian cells to ionizing radiation.

UI	MeSH Term	Description	Entries
D002460	Cell Line	Established cell cultures that have the potential to propagate indefinitely.	Cell Lines,Line, Cell,Lines, Cell
D002843	Chromatin	The material of CHROMOSOMES. It is a complex of DNA; HISTONES; and nonhistone proteins (CHROMOSOMAL PROTEINS, NON-HISTONE) found within the nucleus of a cell.	Chromatins
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
D006224	Cricetinae	A subfamily in the family MURIDAE, comprising the hamsters. Four of the more common genera are Cricetus, CRICETULUS; MESOCRICETUS; and PHODOPUS.	Cricetus,Hamsters,Hamster
D006801	Humans	Members of the species Homo sapiens.	Homo sapiens,Man (Taxonomy),Human,Man, Modern,Modern Man
D000818	Animals	Unicellular or multicellular, heterotrophic organisms, that have sensation and the power of voluntary movement. Under the older five kingdom paradigm, Animalia was one of the kingdoms. Under the modern three domain model, Animalia represents one of the many groups in the domain EUKARYOTA.	Animal,Metazoa,Animalia
D015233	Models, Statistical	Statistical formulations or analyses which, when applied to data and found to fit the data, are then used to verify the assumptions and parameters used in the analysis. Examples of statistical models are the linear model, binomial model, polynomial model, two-parameter model, etc.	Probabilistic Models,Statistical Models,Two-Parameter Models,Model, Statistical,Models, Binomial,Models, Polynomial,Statistical Model,Binomial Model,Binomial Models,Model, Binomial,Model, Polynomial,Model, Probabilistic,Model, Two-Parameter,Models, Probabilistic,Models, Two-Parameter,Polynomial Model,Polynomial Models,Probabilistic Model,Two Parameter Models,Two-Parameter Model
D016012	Poisson Distribution	A distribution function used to describe the occurrence of rare events or to describe the sampling distribution of isolated counts in a continuum of time or space.	Distribution, Poisson