Xeroderma Pigmentosum(XP)

着色性干皮病

• As a result ,person with XP are extremely sensitive to sunlight

• Even very limited exposure to the direct rays of the sun can produce large numbers of dark-pigmented spots on exposed areas of the body and a greatly elevated risk of developing disfiguring and fatal skin cancers.

The mechanism about XP------nucleotide excision repair deficiency(核苷酸切除修复缺陷 )

• When subjected to ultraviolet radiation ,adjacent(相邻的 ) pyrimidines(嘧啶 ) on a DNA strand have a tendency to interact with one another to form a covalent(共价的 ) dimer complex.(example as TT---胸腺嘧啶二具体 )

• Once TT is formed, ultraviolet radiated DNA will not be repaired correctly.

• The replication and the transcription of DNA will be influenced seriously.

• THF II H--- a crucial link between transcription and DNA repair

• XPB and XPD are two subunits of THF II H

nucleotide excision repair

• In persons with XP who carry specific mutations in the XPD gene.

• XPD gene encodes a subunit of the TFII H required for transcription initiation(起始 )

• So, Mutations in XPD could lead to defect(缺陷 ) in both DNA repair and transcription

How to help XP patients?• Some help for XP patients may be on the way in the

form of skin creams that contain DNA repair enzymes.

• The enzyme are contained in liposomes(脂质体 ) that can apparently penetrate (穿过 ) the outer layer of the skin and participate in repair pathways

• XP is a very rare condition ,but colon cancer(结肠癌 ) is relatively common.

• It is estimated that up to 15 percent of colon cancer cases can be attributed to mutations in the genes that encode the proteins required for mismatch repair.

• Mutations that cripple the mismatch repair system inevitably lead to higher mutation rate in other genes because mistakes made during replication are not corrected.