Mutant Mouse Cells Point to a Possible Protein Joining DNA Segments

Sheinin and colleagues, writing in Cell in 1976, studied a mutant strain of mouse cells called ts A1S9 to work out why these cells fail to properly build their DNA at high temperature. The model was cell culture: mouse L cells carrying a temperature-sensitive mutation, meaning a defect that only shows up above a certain temperature.

At the normal working temperature of 38.5°C, these cells synthesized DNA normally for six to eight hours. After that point, they could still make short new strands of DNA — polydeoxyribonucleotide chains roughly a million daltons in molecular weight — but could not stitch these small fragments together into the full-length chromosomal DNA strands a cell needs. The authors say their data are compatible with a model in which a specific protein, sensitive to heat, is responsible for joining newly copied DNA segments into complete chromosomes, though the paper does not identify or isolate that protein.

When the cells were shifted back to a cooler, permissive temperature, they regained the ability to join DNA fragments several hours before their overall DNA synthesis rate returned to normal. As an abstract-only cell biology report from 1976, the paper does not address skin, wounds, or any therapeutic use of DNA fragments.