title: Physiology of the read-write genome.
abstract: Discoveries in cytogenetics, molecular biology, and genomics have revealed that genome change is an active cell-mediated physiological process. This is distinctly at variance with the pre-DNA assumption that genetic changes arise accidentally and sporadically. The discovery that DNA changes arise as the result of regulated cell biochemistry means that the genome is best modelled as a read-write (RW) data storage system rather than a read-only memory (ROM). The evidence behind this change in thinking and a consideration of some of its implications are the subjects of this article. Specific points include the following: cells protect themselves from accidental genome change with proofreading and DNA damage repair systems; localized point mutations result from the action of specialized trans-lesion mutator DNA polymerases; cells can join broken chromosomes and generate genome rearrangements by non-homologous end-joining (NHEJ) processes in specialized subnuclear repair centres; cells have a broad variety of natural genetic engineering (NGE) functions for transporting, diversifying and reorganizing DNA sequences in ways that generate many classes of genomic novelties; natural genetic engineering functions are regulated and subject to activation by a range of challenging life history events; cells can target the action of natural genetic engineering functions to particular genome locations by a range of well-established molecular interactions, including protein binding with regulatory factors and linkage to transcription; and genome changes in cancer can usefully be considered as consequences of the loss of homeostatic control over natural genetic engineering functions.
authors.affiliation: Department of Biochemistry and Molecular Biology, University of Chicago, GCISW123B, 979 E. 57th Street, Chicago, IL 60637, USA jsha@uchicago.edu.
authors.forename: James A
authors.initials: JA
authors.lastname: Shapiro
mesh_terms: D000818:Animals; D005786:Gene Expression Regulation / Q000502:physiology*; D016678:Genome; D006706:Homeostasis / Q000235:genetics* / Q000502:physiology*