A model for repair of radiation‐induced DNA double‐strand breaks in the extreme radiophile Deinococcus radiodurans

Abstract

The bacterium Deinococcus (formerly Micrococcus) radiodurans and other members of the eubacterial family Deinococaceae are extremely resistant to ionizing radiation and many other agents that damage DNA. Stationary phase D. radiodurans exposed to 1.0-1.5 Mrad gamma-irradiation sustains > 120 DNA double-strand breaks (dsbs) per chromosome; these dsbs are mended over a period of hours with 100% survival and virtually no mutagenesis. This contrasts with nearly all other organisms in which just a few ionizing radiation induced-dsbs per chromosome are lethal. In this article we present an hypothesis that resistance of D. radiodurans to ionizing radiation and its ability to mend radiation-induced dsbs are due to a special form of redundancy wherein chromosomes exist in pairs, linked to each other by thousands of four-stranded (Holliday) junctions. Thus, a dsb is not a lethal event because the identical undamaged duplex is nearby, providing an accurate repair template. As addressed in this article, much of what is known about D. radiodurans suggests that it is particularly suited for this proposed novel form of DNA repair.

Oxidative Stress Resistance inDeinococcus radiodurans

“…The homology search by the RecA-DNA filament is encumbered by the small cellular concentration of the target compared to the vast excess of the nontarget DNA along with the low diffusion coefficients of DNA (201). A homologous search conducted under such circumstances would entail a repetitive and futile reinspection of multiple randomly dispersed DNA fragments, making the process of the reconstruction of chromosomes seem like an insurmountable task (415). Several models explain how structural aspects may contribute to the observed rapidity and efficiency of the RecAmediated homology search in D. radiodurans: (i) genome condensation, (ii) ring-like nucleoid morphology, (iii) DNA-membrane association, and (iv) chromosome alignment.…”

“…Murray proposed in 1986 that the error-free repair in D. radiodurans is mediated by some aspect of the nuclear structure that allows the juxtaposition of homologous regions of multiple genome copies so that recombinational exchange can take place (452). Minton and Daly elaborated a model where chromosomes are linked to each other by thousands of Holliday junctions (415). Such a prealignment would ensure immediate access to the substrate during recombinational repair and would thus facilitate the "search for homology."…”

Genome of the Extremely Radiation-Resistant Bacterium Deinococcus radiodurans Viewed from the Perspective of Comparative Genomics

“…Therefore, it may be that D. radiodurans can use redundant information in ways that other organisms do not. An alternative repair model has been postulated for D. radiodurans in which its chromosomes are always aggregated and aligned, thus dramatically simplifying the search for repair templates (51,139) following DNA damage.…”

Predicted highly expressed and putative alien genes of Deinococcus radiodurans and implications for resistance to ionizing radiation damage

“…It was conjectured that, although DEIRA possesses the standard prokaryotic repair repertoire, there must occur intrinsic mechanisms that augment repair (3,5). It is estimated that at least 40% of damaged DNA is degraded, presumably by controlled cellular exonucleases.…”

“…The mechanisms of this resistance are unclear. Our objectives in this paper are to report on predicted highly expressed genes (PHX) and putative alien (PA) genes (see below for formal definitions) and their implications how these genes may help guide research into understanding DEIRA survival through periods of extended ionizing damage and desiccation (2)(3)(4)(5)(6). The complete lists of PHX and PA genes in DEIRA are presented in our ftp site, ftp:͞͞gnomic.stanford.edu͞pub͞ highlyexpressed.…”