Inter-individual variation in DNA repair capacity: a need for multi-pathway functional assays to promote translational DNA repair research.
Why does a constant barrage of DNA damage lead to disease in some individuals, while others remain healthy? This article surveys current work addressing the implications of inter-individual variation in DNA repair capacity for human health, and discusses the status of DNA repair assays as potential clinical tools for personalized prevention or treatment of disease. In particular, we highlight research showing that there are significant inter-individual variations in DNA repair capacity (DRC), and that measuring these differences provides important biological insight regarding disease susceptibility and cancer treatment efficacy. We emphasize work showing that it is important to measure repair capacity in multiple pathways, and that functional assays are required to fill a gap left by genome wide association studies, global gene expression and proteomics. Finally, we discuss research that will be needed to overcome barriers that currently limit the use of DNA repair assays in the clinic.
Department of Biological Engineering, Massachusetts Institute of Technology, Cambridge, MA 02139, USA; Center for Environmental Health Sciences, Massachusetts Institute of Technology, Cambridge, MA 02139, USA.
Zachary D
ZD
Nagel
Department of Biological Engineering, Massachusetts Institute of Technology, Cambridge, MA 02139, USA; Center for Environmental Health Sciences, Massachusetts Institute of Technology, Cambridge, MA 02139, USA.
Isaac A
IA
Chaim
Department of Biological Engineering, Massachusetts Institute of Technology, Cambridge, MA 02139, USA; Center for Environmental Health Sciences, Massachusetts Institute of Technology, Cambridge, MA 02139, USA; Department of Biology, Massachusetts Institute of Technology, Cambridge, MA 02139, USA; The David H. Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, Cambridge, MA 02139, USA. Electronic address: lsamson@mit.edu.
Leona D
LD
Samson
D001681:Biological Assay; D004249:DNA Damage / Q000235:genetics*; D004260:DNA Repair / Q000235:genetics*; D015972:Gene Expression Regulation, Neoplastic; D014644:Genetic Variation; D055106:Genome-Wide Association Study; D006801:Humans; D009369:Neoplasms / Q000209:etiology / Q000235:genetics*; D040901:Proteomics; D057170:Translational Research, Biomedical
DNA repair capacity; Multiplex assays; Personalized disease prevention and treatment