Bloom Helicase & Bloom Syndrome

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Presentation transcript:

Bloom Helicase & Bloom Syndrome Aslı Sahin

Bloom Syndrome (Congenital Telangiectatic Erythema) Dr. David Bloom in 1954. Autosomal Recessive Disease High frequency of breaks and rearrangements in chromosomes Diagnosed in the first few months of life. Very rare  Total 220 cases 1/104 Ashkenazi Jewish person is a carrier of BLMAsh USA & Japan consanguinity Karyotype of a Normal Individual Karyotype of an individual with Bloom Syndrome Amor-Gueret M. Bloom's syndrome. Orphanet Encyclopedia. February 2004

Main Clinical Features short stature photosensitive facial skin lesion & red sun-sensitive skin lesions on the face Narrow Face&Prominent ears Immunodeficiency M/F  infertility/subfertility Predisposition to malignancy earlier (~25yr) &more frequent(x300) Death before 30

Nathan E. Allis et al,The Bloom’s Syndrome Gene Product Is Homologous to RecQ Helicases, Cell Vol 83 , November 17, 1995

Protein : The Bloom (BLM) syndrome protein,1417 aa Gene name: BLM Location: 15q26.1 Protein : The Bloom (BLM) syndrome protein,1417 aa Expression Level: High levels in S phase Localisation: Nuclear Ian D.Hickson et al. RecQ HELICASES: CARETAKERS OF THE GENOME. Nature Reviews- Cancer. Volume 3/ March 2003

Unwinds complementary strands at replication fork Helicases Unwinds complementary strands at replication fork Superfamily II: RecQ Genome Integrity Tumor Suppressor Gene Well-conserved

RecQ Helicase Members in Humans BLM WRN RECQ4 RECQL RECQ5β Bloom’s Syndrome Werner’s Syndrome Rothmund – Thomson Syndrome

Insert Cassettes with viruses Sequence Generate Mutations Insert Cassettes with viruses Compare sequence with Human BLM mutants Choose most similar one Luo, G. et al. Cancer predisposition caused by elevated mitotic recombination in Bloom mice. Nature Genet. 26, 24–429 (2000).

Luo, G. et al. Cancer predisposition caused by elevated mitotic recombination in Bloom mice. Nature Genet. 26, 24–429 (2000).

Why BLM Cause Cancer? 1- Because of its function......

Maintenance of Genome Integrity Ian D.Hickson et al. RecQ HELICASES: CARETAKERS OF THE GENOME. Nature Reviews- Cancer. Volume 3/ March 2003

Why BLM Cause Cancer? 1- Because of its function...... 2- Because of its pathways....

BLM’s Interactions with other Tumor-suppresor Proteins Ian D.Hickson et al. RecQ HELICASES: CARETAKERS OF THE GENOME. Nature Reviews- Cancer. Volume 3/ March 2003

QuestIons ??? References http://www.dnadirect.com/patients/tests/ashkenazi/bloom_syndrome.jsp http://en.wikipedia.org/wiki/Bloom_syndrome http://www.ncbi.nlm.nih.gov/sites/entrez?Db=gene&Cmd=ShowDetailView&TermToSearch=641 http://www.emedicine.com/DERM/topic54.htm http://ghr.nlm.nih.gov/condition=bloomsyndrome http://www.gfmer.ch/genetic_diseases_v2/gendis_detail_list.php?cat3=450 http://www.bio.davidson.edu/Courses/Molbio/MolStudents/spring2003/Baxter/BLMgene.html

THANK YOU FOR YOUR PATIENCE Aslı Sahin