A history of the DNA repair and mutagenesis field

Abstract

Photoreactivation, an enzyme-catalyzed reaction during which two covalently linked pyrimidine dimers in DNA are monomerized and restored to their native conformation was the first DNA repair mechanism to be discovered, an event that transpired in the late 1940’s through the efforts of the American biologist Albert Kelner while at the Cold Spring Harbor Laboratories in upstate New York. The phenomenon was Independently observed by Renato Dulbecco shortly thereafter, then a post-doctoral fellow in Salvador Luria’s Laboratory in Bloomington Indiana. However, Luria and Dulbecco yielded priority to Kelner’s discovery.

Introduction

Aside from my career spent almost exclusively on the study of DNA repair I have long held an abiding interest in the history of this topic, a history that emerged from the study of the effects of radiation on living cells and organisms and the subsequent recognition that DNA is a principal target of the harmful effects of this source of genomic insult. Given the massive literature on any field of intellectual endeavor that accumulates in real time, why tax one’s time and energy with the history of the field? The reality lies in one’s definition of the word “history”. Dictionaries define history as “the branch of knowledge dealing with past events” – or something equivalent. But the fact is that all scientists deal with history on a regular basis. Every paper contributed to the scientific literature of necessity dwells on history, a feature most obviously manifested by references to the literature that are a staple of all publications focused on the announcement of new information. The only feature that distinguishes the documentation of history in a manuscript focused on new information and one that confines itself exclusively to old information is the breadth of time under consideration. Indeed, it would not be unreasonable to replace the title “Introduction” that typically begins most scientific papers contributed to the literature, with “history”.

Having hopefully convinced you that aside from its intrinsic interest to the curious mind, understanding the history of a field of research endeavor is in fact essential to the expansion of information in that field, I invite you to examine the early history of the DNA repair field through a series of articles to be published in DNA Repair, of which this is the first.

Readers familiar with a book that I published 18 years ago entitled Correcting the Blueprint of Life – A Historical Account of the Discovery of DNA Repair Mechanisms [1] will recognize that this article has borrowed heavily from that tome, though this is not a direct reprinting of the chapter on the discovery of photoreactivation. New insights and historical nuances have been added. My motive for rewriting this article stems from the supposition that during the past two decades a new generation of photobiologists and DNA repairologists has presumably joined the ranks of earlier stalwarts of DNA repair and mutagenesis. This, and a series of subsequent historical articles on other DNA repair mechanisms is the primary intended audience of this contribution.

Beginning with Gregor Mendel, biologists interested in examining the nature of genes and inheritance were heavily reliant on the appearance of spontaneous alterations of gene function in experimental subjects. Spontaneous mutations being rare events, the discovery in the late 1920’s by the geneticist Hermann Muller that X-rays greatly enhance the mutation frequency in the fruit fly Drosophila melanogaster was an important milestone in genetics. In fact it earned him a Nobel prize in Physiology or Medicine in 1946.

In due course, the utility of X-rays as an experimental tool to examine the function of genes was broadened to include ultraviolet (UV) radiation as well as chemicals that interact with DNA. These observations stimulated the evolution of a new investigative field characterized by the perturbation of genes by exogenous agents and the examination of the phenotypic consequences thereof – the biological responses to DNA damage. Thus was born a field of experimental investigation now generally referred to as DNA repair. However, biological responses to DNA damage sometimes translate to aspects of DNA metabolism other than the repair of damage – other important sources of mutations.

In 1984, I contributed another volume to the scientific literature called DNA Repair [2], a work that was updated and expanded with co-authors Graham Walker and Wolfram Siede in 1995 as DNA Repair and Mutagenesis [3] and again a decade later with the additional co-authorship of Wolfram Siede, Richard (Rick) Wood, Roger Schultz and Tom Ellenberger in 2005 [4]. In each of these textbooks cellular responses to DNA damage is classified as follows: