Evidence relevant to untargeted and transgenerational effects in the offspring of irradiated parents.

In this article we review health effects in offspring of human populations exposed as a result of radiotherapy and some groups exposed to chemotherapy. We also assess risks in offspring of other radiation-exposed groups, in particular those of the Japanese atomic bomb survivors and occupationally and environmentally exposed groups. Experimental findings are also briefly surveyed.

Error-prone repair and translesion synthesis III: the activation of UmuD (or less is more).

Following DNA damage to Escherichia coli bacteria, RecA protein is activated by binding to single stranded DNA and cleaves its own gene repressor (LexA protein). Two papers from Graham Walker's laboratory showed that several bacterial genes in addition to RecA are repressed by the LexA repressor and are inducible following DNA damage [C.J.

Error-prone DNA repair and translesion DNA synthesis. II: The inducible SOS hypothesis.

Evelyn Witkin hypothesized in 1967 that bacterial cell division is controlled by a repressor which, like the lambda repressor, is inactivated by a complex process that starts with the presence of replication-blocking lesions in the DNA. She further suggested that this might not be the only cellular function to show induction by DNA damage. Three years later, Miroslav Radman, in a privately circulated note, proposed that one such function might be an inaccurate (mutation-prone) DNA polymerase under the control of the recA and lexA genes.

Error-prone DNA repair and translesion synthesis: focus on the replication fork.

Dean Rupp and Paul Howard-Flanders showed that, following exposure to ultraviolet light, bacteria deficient in nucleotide excision repair synthesised DNA with minimal delay and in pieces roughly the size of the distances between pyrimidine dimmers. The discontinuities or gaps between these pieces were subsequently sealed. This led directly to the hypothesis of translesion synthesis.

Strange goings-on in the mouse germ line.

It is a conventional paradigm that mutagens lead to changes in nucleotide sequence when the cell attempts to repair or replicate lesions in DNA (such as adducts or strand breaks) that have been produced by the mutagens or their metabolites. The resulting changes are located at (or very near) the sites of the initial damage. This is the underlying theory behind mutational spectra work, but how general is it in vivo? Work with ionising radiation has shown that there are interesting things going on in the mouse germ line that do not fall within the conventional paradigm.

DNA polymerase V-dependent mutator activity in an SOS-induced Escherichia coli strain with a temperature-sensitive DNA polymerase III.

The temperature-sensitive DNA polymerase III (Pol III) encoded by the dnaE486 allele confers a spontaneous mutator activity in SOS-induced bacteria that is largely dependent upon DNA polymerase V (Pol V), encoded by umuD, C. This mutator activity is influenced by the defective proof-reading sub-unit of Pol III encoded by the dnaQ905 (mutD5) allele arguing that Pol V is most likely fixing mutations arising from mismatched primer termini produced by Pol III(486). The size of the dnaQ effect is, however, modest leaving open the possibility that Pol V may be responsible for some of the mutator effect by engaging in bursts of processive activity.

Sequence analysis and phenotypes of five temperature sensitive mutator alleles of dnaE, encoding modified alpha-catalytic subunits of Escherichia coli DNA polymerase III holoenzyme.

In the 1970s, several thermosensitive alleles of dnaE (encoding the alpha-catalytic subunit of pol III) were isolated. Genetic characterization of these dnaE mutants revealed that some are mutator alleles at permissive temperature. We have determined the nucleotide changes of five such temperature sensitive mutator alleles (dnaE9, dnaE74, dnaE486, dnaE511, and dnaE1026) and find that most are single missense mutations.