Molecular characterization of an acidic region deletion mutant of Cockaynesyndrome group B protein

Cockayne syndrome (CS) is a human genetic disorder characterized by post-na tal growth failure, neurological abnormalities and premature aging. CS cell s exhibit high sensitivity to UV light, delayed RNA synthesis recovery afte r UV irradiation and defective transcription-coupled repair (TCR). Two gene tic complementation groups of CS have been identified, designated CS-A and CS-B, The CSB gene encodes a helicase domain and a highly acidic region N-t erminal to the helicase domain. This study describes the genetic characteri zation of a CSB mutant allele encoding a full deletion of the acidic region , We have tested its ability to complement the sensitivity of UV61, the ham ster homolog of human CS-B cells, to UV and the genotoxic agent N-acetoxy-2 -acetylaminofluorene (NA-AAF), Deleting 39 consecutive amino acids, of whic h similar to 60% are negatively charged, did not impact on the ability of t he protein to complement the sensitive phenotype of UV61 cells to either UV or NA-AAF, Our data indicate that the highly acidic region of CSB is not e ssential for the TCR and general genome repair pathways of UV- and NA-AAF-i nduced DNA lesions.