Overview human DNA Repair Genes and Mechanisms

Overview of human DNA Repair Genes and Mechanisms


Robert Gorter, MD, PhD.

Emeritus Professor, University of Calfornia San Francisco Medical School (UCSF)

May 26th, 2022


DNA Repair Mechanisms and Pathways in Cancer Therapy and Resistance

Ronen A, Glickman BW. Human DNA repair genes. Environ Mol Mutagen. 2001;37(3):241-83. DOI: 10.1002/em.1033. PMID: 11317342.


DNA repair systems are essential for the maintenance of genome integrity. Consequently, the dysregulation of repair genes can be expected to be associated with significant, detrimental health effects, which can include an increased prevalence of birth defects, and enhancement of cancer risk, and an accelerated rate of aging. Although original insights into DNA repair and the genes responsible were largely derived from studies in bacteria and yeast, well over 125 genes directly involved in DNA repair have now been identified in humans, and their cDNA sequence established. These genes function in a diverse set of pathways that involve the recognition and removal of DNA lesions, tolerance to DNA damage, and protection from errors of incorporation made during DNA replication or DNA repair. Additional genes indirectly affect DNA repair, by regulating the cell cycle, ostensibly to provide an opportunity for repair or to direct the cell to apoptosis. For about 70 of the DNA repair genes listed in Table I, both the genomic DNA sequence and the cDNA sequence and chromosomal location have been elucidated. In 45 cases single-nucleotide polymorphisms have been identified and, in some cases, genetic variants have been associated with specific disorders. With the accelerating rate of gene discovery, the number of identified DNA repair genes and sequence variants is quickly rising. This report tabulates the current status of what is known about these genes. The report is limited to genes whose function is directly related to DNA repair.


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We investigated alteration in DNA repair during therapy with a plant-derived immunomodulator. 14 patients with advanced breast cancer were treated parenterally with Iscador, an extract of Viscum album (mistletoe). As a parameter for measurement of DNA repairs the incorporation of (3H) thymidine into the DNA of unstimulated lymphocytes after ultraviolet light (UV) damage was taken. The DNA repair values in the patients were very low before treatment and on day 1: on average 16% of those in a healthy control population. Values started to increase on day 2 and on days 7-9 were on average 2.7 times higher than before treatment. 12/14 patients showed an improvement in repair. The values of spontaneous DNA synthesis were not altered during the treatment. We suggest that the increase in DNA repair could be due to a stimulation of repair enzymes by lymphokines or cytokines secreted by activated leukocytes or an alteration in the susceptibility to exogenic agents resulting in less damage.

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