Trichothiodystrophy associated with photosensitivity, gonadal failure, and striking osteosclerosis.

Three new unrelated cases of PIBIDS (Photosensitivity, Ichthyosis, Brittle, sulfur-deficient hair [trichothiodystrophy], Impaired intelligence, Decreased fertility, and Short stature) are reported. Decreased survival of skin fibroblast lines after UVB exposure was found. All three male patients had hypogonadism and primary end-organ gonadal failure. Striking osteosclerosis was present in all three patients. To the best of our knowledge the third patient is the first reported case of a black man with PIBIDS.

Synergistic interaction between UV and ionizing radiation in wild-type Schizosaccharomyces pombe.

A synergistic effect of combined UV and gamma-ray exposure was observed for inactivation of wild-type Schizosaccharomyces pombe. A recombinational repair process, known to be important in restitution of damage induced by both radiations, appears to be involved; a radiation-sensitive mutant defective in this repair pathway showed essentially no synergistic interaction between UV and gamma-rays. Recovery from the synergistic effect of pre-exposure in wild-type cells did not display the expected fast gamma-recovery and slow UV-recovery kinetics previously observed for regain of resistance to further exposure to the same radiation. Rather, UV-irradiated cells recovered quickly from synergistic inactivation on subsequent gamma-exposure, while gamma-irradiated cells recovered UV-resistance slowly. Recovery from synergism thus appears to reflect the nature of the second, and not the initial, radiation.

Slow UV-recovery and fast gamma-recovery in wild-type Schizosaccharomyces pombe.

The time course of recovery in UV- or gamma-irradiated wild-type Schizosaccharomyces pombe has been determined by fractionated dose experiments and by measuring the rate at which the "resistant shoulder" of the survival curve was regained during post-irradiation incubation in growth medium. The kinetics of recovery after UV-irradiation were different from those after gamma-irradiation, and may be described as due to a fasy gamm-repair and a relatively slow UV-repair process. In fractionated dose experiments, for single exposures which gave about 10% survival, gamma-repair was rapid (t1/2 congruent to 2 h), began immediately, and was essentially complete within 3 h. UV-repair, in contrast, showed a lag of about 5h and was relatively show (t1/2 congruent to 10h). The nature of the recovery response was analyzed from the survival curves at intermediate times; recovery was evident as the reappearance of a shoulder. A heterogenous recovery was evident after UV-irradiation; after a 5 h lag, a progressively increasing fraction of the survivors regained UV-resistance, which suggested that some critical event or rate-limiting step was involved. A requirement for post-irradiation protein synthesis for activity of a recombinational repair pathway on UV-damage may be a factor in the UV-recovery lag. A homogeneous recovery response, however, was observed in gamma-irradiaged cells.

Effect of protein synthesis inhibition on recovery of UV- and gamma-irridated Schizosaccharomyces pombe from repair inhibition by caffeine.

The progress of repair in Schizosaccharomyces pombe may be followed during post-irradiation incubation by measuring, after various intervals, the ability of UV- or gamma-irradiated cells to avoid enhanced lethality when exposed to the repair inhibitor caffeine (Gentner and Werner, 1975). This technique has now been used to investigate the effect of inhibition of protein synthesis on repair of UV- and gamma-irradiation-induced damage in this organism. When protein synthesis was inhibited with cycloheximide in UV-irradiated wild-type cells, only a small amount of recovery from caffeine inhibition occurred; this indicated that post-irradiation protein synthesis was required for repair, and in particular for the recombinational repair pathway, which is a major mechanism for repair of UV damage in this organism. In gamma-irradiated wild-type cells, inhibition of post-irradiation protein synthesis reduced the rate of recovery from repair inhibition by caffeine, but full recovery from caffeine-sensitive damage did occur at longer incubation times. We attribute the reduction in rate to the effect of protein synthesis inhibition on the recombinational repair pathway, because this pathway is known to be involved in the repair of both gamma-ray and UV damage. The recovery that took place at the slower rate must reflect a caffeine-sensitive pathway which is involved only in repair of gamma-ray damage and which does not require post-irradiation protein synthesis for activity.

Repair in Schizosaccharomyces pombe as measured by recovery from caffeine enhancement of radiation-induced lethality.

Inhibition of DNA repair by caffeine is manifested in Schizosaccharomyces pombe wild-type cells as an enhancement of UV- or gamma-irradiation-induced lethality. The progress of DNA repair processes involving one or more caffeine-sensitive steps may be conveniently followed by measuring the concomitant decrease of this lethal enhancement effect. By measuring, during post-irradiation incubation, the ability of cells to overcome susceptibility to repair inhibition by caffeine, we have determined the time course and requirements for repair in S. pombe. Recovery began immediately and took 150-200 min after gamma-irradiation and more than 500 min after UV-irradiation, for exposures which gave about 10% survival in the absence of caffeine. An incubation medium capable of supporting growth was required for caffeine-sensitive repair; no recovery occurred under liquid holding conditions. Survival curves after various recovery times indicated that a logarithmic phase cell population was homogeneous with respect to caffeine-sensitive repair of both UV- and gamma-ray-induced damage. Recovery from caffeine inhibition was compared for cells of different physiological states (logarithmic and stationary phase); although the importance of the physiological state was not the same for the two types of radiation, recovery was found to occur more rapidly in the more radiation-resistant state, in each case.