1. Bloom Helicase & Bloom Syndrome
Aslı Sahin

2. 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

3. 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

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

5. 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

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

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

8. 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).

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

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

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

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

13. 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

14. QuestIons ???
References

15. THANK YOU FOR YOUR PATIENCE
Aslı Sahin