Understanding the Role of Photolyases: Photoprotection and Beyond

May 2017 | Volume 16 | Issue 5 | Supplement | 61 | Copyright © 2017

Neal Bhatia MD,a Brian Berman MD PhD,b Roger I. Ceilley MD,c and Leon H. Kircik MDd

aTherapeutics Clinical Research, San Diego, CA bUniversity of Miami Miller School of Medicine, Miami, FL Center for Clinical and Cosmetic Research, Aventura, FL Skin & Cancer Associates, LLP, Miami, FL cDermatology P.C., West Des Moines, IA dIcahn School of Medicine at Mount Sinai, NY Indiana School of Medicine, Indianapolis, IN Physicians Skin Care, PLLC, Louisville, KY DermResearch, PLLC, Louisville, KY Skin Sciences, PLLC, Louisville, KY

Abstract

The limitations of photoprotection modalities have been the inability to arrest the progression of photodamage. Chemoprevention strategies involving a sunscreen has been incomplete because of the need to induce sustained repair of mutations and slow carcinogenesis. Photolyases, or photoreactivation enzymes, serve the role of repairing mutations and damage to DNA induced by ultraviolet (UV) radiation and therefore influence the initiation phases of carcinogenesis. As these enzymes are absent in humans, exogenous forms have been manufactured and are now utilized in topical agents to supplement and augment the innate repair mechanisms that are mostly inefficient.

J Drugs Dermatol. 2017;16(5 Suppl):61-66.

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INTRODUCTION

If there is a cookbook in Dermatology, the essential ingredient in every recipe is sunscreen. Patients presenting with acne, rhytides, melasma, actinic keratoses, or anything else within a dermatology office all need and should receive proper sunscreen and education. The concept of photoprotection is often the last but most resonating message that patients are given before they leave the clinic: “Don’t forget to wear sunscreen” … “wear it every 2 hours while outdoors” ... ”protecting yourself from the sun will significantly reduce your skin cancer risk, prevent the pigmentation from getting worse, keep you looking younger…” and so on. A common analogy shared with patients and colleagues is that sunscreen is like toothpaste for the skin: we brush our teeth twice a day and after every meal, so the same should go for applying sunscreen routinely at breakfast and lunch and while outdoors. Excessive sun exposure could be the same as eating too many sweets. In addition, dermatologists not only treat but also provide methods to prevent consequences from cumulative UV exposure, like brushing our teeth every day is meant to prevent dental problems. We don’t just brush one tooth, we brush them all, and just like cavities, where we see one, there is a good chance that more are on the way, one actinic keratosis (AK) or lentigo signals an entire field of photodamaged skin at risk, therefore necessitating full coverage of a daily sunscreen.Until recently, our topical photoprotection modalities have had the limitations of being only for protection without any impact on or utility in reversing the process of what photodamage does to the skin. Cosmetic benefits from additives to commercial sunscreens such as retinol, antioxidants, or alpha-hydroxyacids and similar ingredients, have their role in the treatment of photoaging but are not proven to slow the progression to actinic keratosis and skin cancer simply because their effects are primarily on epidermal differentiation or improvement in collagen homeostasis. Having additional ingredients in our toolbox that could help address the progression of actinic damage would make daily application of sunscreen a more meaningful option for the high-risk patients, sun worshippers, transplant patients, and everyone in between. Photolyases, a type of photo reactivation enzyme, serves the role of repairing DNA mutations and damage induced by UV radiation and therefore has the potential to influence the development of carcinogenesis. As these enzymes have not been identified in humans, exogenous forms have been manufactured and are now utilized in topical agents to supplement and augment the innate repair mechanisms that are not completely efficient. 2In this supplement, there will be an introduction to the science of photolyases including a historic review, elucidation of their mechanisms of action, and effects on the process of

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