Xeroderma Pigmentosum
Biology 111 Extra Credit Research Paper
Anna Elizabeth Cummings
Bio ID: 81813
Xeroderma pigmentosum is a terminal genetic disease that usually shows its affects in
children. The chance of having xeroderma pigmentosum is only 1 in 70,000 (Rasko, Istvan.)
Since the chances of getting xeroderma pigmentosum are so low it comes as no surprise that the
disease is a recessive autosomal recessive genetic disease. Therefore, the child would only have
the disease if both parents were carriers or in the more unlikely case, both parents had the disease
themselves. In the case of xeroderma pigmentosum, the disease is characterized by a mutation in
one of a number of genes involved in nucleotide excision repair (Wright). In simpler terms, when
the DNA is being broken apart and then copied for replication, the repair mechanism does not
work properly. The fact that the specific nucleotides do not get repaired causes this disease to
increase the risks of skin cancer, melanoma, and reducies life expectancy. Because the disease is
genetic and is known to reduce the life expectancy, the disease is most commonly seen in
children rather than in adults. Xeroderma pigmentosum affects more people than just the ones
medically suffering. Families and friends have to alter their lives for the sake of safety for the
child or person in their life battling xeroderma pigmentosum. The USA Today had a fairly recent
article about HOPE week and the Yankees contributing to Xeroderma pigmentosum in children.
The article states that, “Kids who have XP (xeroderma pigmentosum) live upside-down lives,
night is day and day is night.” Because the disease is so rare and not a lot of information is
known, there is no cure. But, there is scientific information dealing with the specifics of the
damaged repair mechanisms that cause this terminal life altering disease.
When DNA is being replicated mistakes are sometimes made. These mistakes are
normally fixed by a nucleotide repair mechanism, but there are multiple types of repair
mechanisms. The mechanism that is involved with xeroderma pigmentosum is the excision
repair which is a common form of nonspecific repair (Raven). Overall, the nonspecific repair
works the same as any other repair system. When a damaged region is found, the repair
mechanism removes the damaged nucleotide and then replaces it with the correct nucleotide. It is
believed that the damage is caused by ultraviolet light which is why skin cancer is such a threat
to those affected by xeroderma pigmentosum. Damage is not just to a couple of nucleotides but
affects the helix as well. The damage is largely a matter of helix-distoring lesions, and a large
number of natural and synthetic chemicals also react with DNA to distort the helix (Rasko,
Istvan). Because the disease affects nucleotides and the helix with irreversible damage, the
severity of xeroderma pigmentosum is intense.
There are two types of xeroderma pigmentosum, classical and variant. In classical
xeroderma pigmentosum cases, the capacity to excise the UV-induced lesions from DNA is
reduced or abolished (Rasko, Istvan). More specifically, before the repair mechanism is needed
and before DNA is replicated there is a process of loosening the tight chromatin structure that is
wound of DNA strands. Classical xeroderma pigmentosum is unique in that it has defects
associated with the process of unwinding and separating DNA strands so that excision repair
enzymes can get to the damage and remove it (Rasko, Istvan).There is also the variant form of
xeroderma pigmentosum. This form has problems in the cell’s replicative machinery that deals
with damage which has not been repaired (Rasko, Istvan). When DNA is replicated, DNA
polymerases check the work of replication for errors. In variant xeroderma pigmentosum, the
DNA polymerases pause at the UV damage sites for an unusually long time (Rasko, Istvan).
Because the polymerases pause for an extra amount of time, their systemic cycle is disrupted and
they are more likely to make more errors.
As previously discussed, xeroderma pigmentosum has problems with the excision repair.
In normal DNA syntheses, the excision repair follows three steps. The first step is recognition of
the damaged nucleotides. Secondly, there is the removal of the damaged region. Lastly, the
resynthesis uses the information on the undamaged strand as a template (Raven). Each of these
steps is equally important in order to ensure that the individual is healthy, but there is more than
this broad spectrum. There are several polymerases and other contributors to this delicate
process. The first two steps are the recognition of a problem and the excision of the damaged
nucleotides. This involves an UvrABC complex. The UvrABC complex binds to the damaged
DNA and cleaves a single strand on either side of the damage then removes it (Raven). This
complex is only seen in the first two steps of excision repair but there are also two DNA
polymerases that help the process of step 3, the synthesis stage. DNA polymerases I or DNA
polymerases II replace the damaged DNA and restores the original information in the damaged
strand by using the complementary strand (Raven). This gives the information how repair is
supposed to happen, but in xeroderma pigmentosum the repair is inadequate which causes
harmful effects.
Those who know the basics of xeroderma pigmentosum are knowledgeable in the fact
that the disease causes an increase in skin cancer risks. But there are also progressive
neurological problems as well. These include: developmental difficulties, mental retardation, and
hearing loss that can eventually lead to deafness ( xps.org). This implies that the people who
suffer from this disease do not have a full quality of life. Currently the disease is not curable
because the damage is irreversible. But many families hope that one day modern science can
come up with an effective method of curing this genetic disease. While there is not a cure there
are some therapies that are possible for some patients.
With the help of modern medicine, there are only two therapies that can be used to help
xeroderma pigmentosum patients but are still not guaranteed to cure the disease. The first type of
therapy is known as molecular or protein therapy. For patients with classical xeroderma
pigmentosum, a cream of liposomes containing very small bacterial DNA repair enzymes is
rubbed onto the skin of the patient, the skin absorbs the lotion like medicine and skin cells start
repairing the damaged cells (Rasko, Istvan). This type of therapy really only helps with skin cells
and does not deal with the neurological effects of the disease, but the therapy can help reduce the
risks of skin cancer. The second therapy is a type of gene therapy that has not been attempted
much. There is an extra normal copy of the defective gene that is inserted into the cell and this
causes there to be an artificial normal gene in action with the two abnormal genes the person
inherited from their parents (xps.org). These therapies are either too new to see any real results
or they only improve the quality of life for the children that suffer from xeroderma pigmentosum.
The disease xeroderma pigmentosum is a death sentence to almost every child that
inherits the disease from their parents. But one child was different. Kevin Swinney is 35 years
old and he has survived the disease. He was diagnosed at 8 months old and has had many
procedures over the course of his life to remove melanomas and other skin problems associated
with the disease (xps.org). While Kevin has been the inspiration to all children diagnosed with
xeroderma pigmentosum, most will not be as lucky as Kevin. The disease cripples one of the
most vital parts of life; the replication of DNA and more specifically the repair nucleotides. The
disease uses UVs to cause the damage and distort the helix and increases skin cancer risks along
with neurological disorders. Xeroderma pigmentosum is a recessive autosomal genetic disease
that no child chooses to have; the disease turns their lives up-side down and ends in a sad,
painful way.
References Cited
McCarthy, Michael. “Yankees’ open their hearts’ during HOPE Week at Stadium.” USA Today.
27 Jul. 2009: Web. 5 Apr. 2010.
Rasko, Istvan, and C. Stephen Downes. Genes in Medicine.London: Chapman & Hall, 1995
Raven, Johnson, et al. Biology. New York: McGraw Hill, 2008.
Wright, Alan, and Nicholas Hastie. Genes and Common Disease. Cambridge: Cambridge
University Press, 2007.
Xps.org. 14 Jan. 2010. Xeroderma Pigmentosum Society, Inc. 5 Apr. 2010. <http://www.
xps.org>