This web page was produced as an assignment for Genetics 677, an undergraduate course at UW‐Madison.
The Bloom's Syndrome gene product is homologous to RecQ helicases.
Ellis
NA, Groden
J, Ye
TZ, Straughen
J, Lennon
DJ, Ciocci
S, Proytcheva
M, German
J.
Laboratory of Human Genetics, New York Blood Center, New York 10021, USA.
Laboratory of Human Genetics, New York Blood Center, New York 10021, USA.
As an extremely rare inherited
disorder, Bloom’s syndrome (BSyn) is not well-known to most people. Before this study
was conducted, the BLM gene was known to be located on chromosome 15. This study was intended to identify and study the BLM
gene at the molecular level. Ellis et al. were able to identify BLM
gene to encode a 1417 amino acid peptide which is
homologous to RecQ helicases. The BLM
gene product is homologous to motifs in the ReqQ helicases, a subfamily of DExH
box-containing DNA and RNA helicases. The authors were able to conclude that
BLM protein has DNA-dependent ATPase and DNA helicase activities based on the
homology of BLM to RecQ and RECQL (a human gene that is possesses DNA-dependent
ATPase, DNA helicase, and 3’-5’ single-stranded DNA translocation activities). In
addition, they pointed out that the high frequency of intra- and inter-chromosomal
exchanges is least likely to be caused by defective DNA repair pathway or
repair enzymes. Since this paper was published back in 1995, when BS was
well-studied, further investigations need to be carried out to validate this hypothesis.
Indeed, a recent study suggested that the absence of BLM can affect the cells’
choice in repairing double strand break repairs, specifically BLM knock out
will prompt cells to use homology repair which is likely to cause deletions in
chromosome [2].
Based on the results obtained from the study, they asserted that BS is an autosomal recessive disorder that has “high penetrance and expressivity”. People diagnosed with BS share the same phenotypes-short stature, facial sun sensitivity, predisposition to cancer development and many others- regardless of their nationality or race. Hence, the authors attributed this phenomenon to the high mutation rates in BS cells which then leads to loss of function of BLM gene products.
Based on the results obtained from the study, they asserted that BS is an autosomal recessive disorder that has “high penetrance and expressivity”. People diagnosed with BS share the same phenotypes-short stature, facial sun sensitivity, predisposition to cancer development and many others- regardless of their nationality or race. Hence, the authors attributed this phenomenon to the high mutation rates in BS cells which then leads to loss of function of BLM gene products.
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References:
1) Ellis, N.A. et al. (1995). The Bloom's syndrome gene product is homologous to RecQ helicases. Cell. 83(4):655-66.
2) Wang, Y. et al. (2010). Depletion of the bloom syndrome helicase stimulates homology-dependent repair at double-strand breaks in human chromosomes. DNA repair [Internet]. Retrieved March 7, 2011 from http://www.sciencedirect.com/science?_ob=ArticleURL&_udi=B6X17-52403R2-1&_user=443835&_coverDate=02%2F05%2F2011&_rdoc=1&_fmt=high&_orig=gateway&_origin=gateway&_sort=d&_docanchor=&view=c&_acct=C000020958&_version=1&_urlVersion=0&_userid=443835&md5=e5dbde42ad0808a32eaece276f5de472&search
2) Wang, Y. et al. (2010). Depletion of the bloom syndrome helicase stimulates homology-dependent repair at double-strand breaks in human chromosomes. DNA repair [Internet]. Retrieved March 7, 2011 from http://www.sciencedirect.com/science?_ob=ArticleURL&_udi=B6X17-52403R2-1&_user=443835&_coverDate=02%2F05%2F2011&_rdoc=1&_fmt=high&_orig=gateway&_origin=gateway&_sort=d&_docanchor=&view=c&_acct=C000020958&_version=1&_urlVersion=0&_userid=443835&md5=e5dbde42ad0808a32eaece276f5de472&search