title: Analysis of DNA replication damage bypass and its role in immunoglobulin repertoire development.
abstract: Cells possess very effective mechanisms for repairing DNA damage. However, in some circumstances repair cannot be carried out before passage of a replication fork, leading to polymerase stalling and an unreplicated gap. Left unrepaired, such gaps will lead to misegregation of genetic information or apoptosis. Cells can ensure that replication is completed by bypassing the damaged bases in the DNA template either directly by translesion synthesis or indirectly by employing an alternative undamaged template. This cellular activity, originally termed post-replication repair is now often referred to as replication damage bypass. Extensively studied in bacteria and yeast, replication damage bypass is now receiving much attention in higher eukaryotes because of its close link to mutagenesis and genetic instability. Work in DT40 has given many insights into the roles of and relationships between the genes involved in DNA damage tolerance and recombination, not least because the cell line can tolerate disruption of many genes that result in early embryonic lethality in mice. In this review we examine current thinking about vertebrate replication damage bypass in the context of studies in bacteria and yeast. We focus particularly on the contribution made by DT40 to these studies and discuss how immunoglobulin diversification in this cell line can contribute to our understanding of replication damage bypass in vertebrates.
authors.affiliation: M.R.C. Laboratory of Molecular Biology, Hills Road, Cambridge CB2 2QH.
authors.forename: Julian E
authors.initials: JE
authors.lastname: Sale
authors.forename: Anna-Laura
authors.initials: AL
authors.lastname: Ross
authors.forename: Laura J
authors.initials: LJ
authors.lastname: Simpson
mesh_terms: D000818:Animals; D001402:B-Lymphocytes; D002460:Cell Line; D002645:Chickens; D004249:DNA Damage; D004261:DNA Replication; D004926:Escherichia coli / Q000235:genetics; D007136:Immunoglobulins / Q000235:genetics*; D016296:Mutagenesis
chemical_list: D007136:Immunoglobulins