EVIDENCE THAT THE PRODUCT OF THE XRS GENE IS PREDOMINANTLY INVOLVED IN THE REPAIR OF A SUBSET OF RADIATION-INDUCED INTERPHASE CHROMOSOME BREAKS REJOINING WITH FAST KINETICS

We classified interphase chromosome breaks into alpha and beta forms t o study the requirement for the xrs gene product in the repair of each of these forms of damage. The alpha form of damage comprises radiatio n-induced interphase chromosome breaks whose rejoining is slow and sen sitive to treatment with beta-arabinofuranosyladenine (beta-araA), whe reas the beta form of damage comprises interphase chromosome breaks wh ose rejoining is fast and sensitive to treatment in hypertonic medium. Interphase chromosome breaks of the a form are visualized in plateau- phase cells by premature chromosome condensation (PCC) carried out in the absence of any treatment during the condensation period. More inte rphase chromosome breaks of the alpha form can be uncovered by treatme nt with beta-araA during the period of PCC. Interphase chromosome brea ks of the beta form are not visualized in experiments using standard P CC protocols but can be uncovered by treatment in hypertonic growth me dium during the period allowed for PCC. In the present report, we show that the yield of interphase chromosome breaks of the alpha form is s imilar in CHO and xrs-5 cells and demonstrate that xrs-5 cells rejoin this type of interphase chromosome breaks with an efficiency similar t o that observed in repair-proficient CHO cells. Furthermore, we provid e evidence supporting the notion that xrs-5 cells are deficient in the rejoining of the beta form of interphase chromosome breaks. These res ults strongly suggest that the product of the xrs gene is required pre dominantly in the repair of the beta form of interphase chromosome dam age and emphasize the need for discrimination between different forms of interphase chromosome breaks in irradiated cells.