UV DNA Repair

Question 1

UVR effects on the skin

Answer 1

Damage to DNA, RNA, lipids and proteins

Pro-inflammatory effects

Immunosuppressive effects

Induction of Innate defenses

Induction of apoptosis

Vit D Synthesis

Question 2

UVR and Vitamin D

Answer 2

Induces non-enzymatic synthesis of cholecalciferol (VitD3) and ergocalciferol (VitD2) -> both converted to active forms in liver and kidneys

Question 3

DNA damage induced by UVR

Answer 3

Thymine dimers (UBV)

Pyrimidine-6-4-pyrimidone (UBV)

Hydroxyguanosine (UVA and singlet oxygen)

Question 4

UVR Proinflammatory effects

Answer 4

mediated by primary and secondary cytokines and lipid mediators.

Erythema, sunburn cells, potentiation of other types of cutaneous inflmmation (adhesion molecule induction, cytokine and chemokine release)

Question 5

Important mediators released by UVR

Answer 5

Primary: IL-1, TNFa
Secondary - IL-6, IL-8, IL-10, GM-CSF

Lipid mediators, growth factors and tumor progression factors, and histamine

Question 6

UVR induced immunosuppression

Answer 6

decreases Langerhans cell population

Induces inhibitory cytokine network - IL10, TH2 cytokine pattern

Tolerance induced by suppressor cells (Treg, NK cells)

Not inhibited by high melanin content

Question 7

Skin defenses against ultraviolet radiation

Answer 7

Apoptosis of cells with DNA damage
DNA repair
Defenses against reactive oxygen
melanin

Question 8

Disorder of defective DNA repair

Answer 8

Xeroderma pigmentosum -> family of diseases in which defects in DNA repair lead to premature aging and fatal induction of UVR-induced skin cancers

Question 9

DNA repair enzymes

Answer 9

Damage recognition: XPC
Unwinding of DNA helix: XPA, XPB, XPD
Incision and release of nucleotides: XPB, XPD, XPF, XPG
Gap filing and ligation: PCNA, DNA polumerase, RPA

Excision of mutated strand:
UVR ABC nuclease

Repair replication: DNA polymerase

Rejoining: DNA ligase

Question 10

Defenses against reactive oxygen in the epidermis

Answer 10

• Peroxidases and catalases
• Superoxide dysmutase
• Glutathione reductase
• Thioredoxin reductase

Question 11

Genes that control pigmentation

Answer 11

Lots! 
Tyrosinase: Rate limiting, OCA
TRP-2 and 1: eumelanin
pink: transport
silver: matrix protein
MC1-R, ASP: eu vs pheo melanin

Question 12

Pigment control?

Answer 12

SLC24A5 - K-dependent Na/Ca ion exchanger
Explaons European/African differences in pigmentation (up to 40%)

SLC45A2 - MATP, marker for caucasians

Question 13

Mutations in genes that control pigmentation

Answer 13

Humans and mice: Oculocutaneous Albinism (OCA)

• OCA I: Tyrosinase
• OCA II: Pink
• OCA III: Tyrp 1
• OCA IV: MATP

Mice:
-Agouti: Experession of agouti-signaling protein

Question 14

Photodermatoses

Answer 14

-Idiopathic probably immunologic
Solar urticaria, PMLE, actinic prurigo
-DNA repair Defects
		Xeroderma pigmentosum
-Chemical photosensitivity
		Drug induced
		Porphyria
-Photoaggrevated dermatoses
		Psoriasis
		Atopic Dermatitis

Question 15

Connective tissue diseases

Answer 15

Lupus Erythematosus
Dermatomyositis
Mixed Connective Tissue Disease (MCTD or Sharp’s
Syndrome)

Question 16

UV phototherapy?

Answer 16

Treatment for extensive psoriasis and atopic dermatitis, repigmentation of vitiligo, mastocytosis, cuteneous T-cell lymphoma