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Eukaryon

Class Year

Lisa Jeziorny 2007

Lindsey McCurdy 2006

Katie Michael 2007

Jennifer Riddle 2007

Kim Silvers 2007

Keywords

Werner Syndrome

Abstract

Werner Syndrome is an autosomal recessive disease characterized by genomic instability, accelerated telomere shortening, and premature aging. Also, Werner Syndrome patients experience increased cancer rates, believed to be directly related to the lack of interaction between the WRN gene and tumor suppressor gene p53. The WRN gene consists of three identical molecules and has both exonuclease and helicase activity, which work together in opposite directions. WRN has been shown to stimulate polymerase â, needed in DNA repair. WRN helicase activity can also bind and degrade G-quadruplexes, which inhibit transcription. Studies show that the tumor suppressor gene p53 co-localizes with WRN during the S phase, inhibiting the exonuclease activity of WRN, and dulling WRN’s helicase ability to unwind Holliday Junctions; thus, revealing the regulation of WRN function by p53 is important for genomic stability. WRN also interacts with TRF2. TRF2 binds to DNA, attracts WRN, and stimulates the folding over of the 3’ overhang of telomeres. Absence of WRN leads to telomere loss and chromosomal fusion which lead to genome instability, accumulation of mutations, and thus cancer. The lack of WRN leads to premature senescence and exhibition of clinical symptoms of aging, even though 91% of RNA pol II transcription genes are expressed similarly to normal aging cells. The purpose of this review is to summarize current literature concerning the molecular pathways of Werner Syndrome.

Disclaimer

Eukaryon is published by students at Lake Forest College, who are solely responsible for its content. The views expressed in Eukaryon do not necessarily reflect those of the College. Articles published within Eukaryon should not be cited in bibliographies. Material contained herein should be treated as personal communication and should be cited as such only with the consent of the author.