Genomic instability and cancer: lessons from analysis of Bloom's syndrome

2009 ◽  
Vol 37 (3) ◽  
pp. 553-559 ◽  
Author(s):  
Miranda Payne ◽  
Ian D. Hickson
Keyword(s):  
Genomic Instability ◽  
Mitotic Chromosome ◽  
Genetic Defect ◽  
Autosomal Recessive Disorder ◽  
Recq Helicase ◽  
Bloom's Syndrome ◽  
Binding Partners ◽  
Bloom’S Syndrome ◽  
Syndrome Protein ◽  
Blm Gene

Bloom's syndrome (BS) is a rare autosomal recessive disorder characterized by genomic instability and cancer predisposition. The underlying genetic defect is mutation of the BLM gene, producing deficiency in the RecQ helicase BLM (Bloom's syndrome protein). The present article begins by introducing BLM and its binding partners before reviewing its known biochemical activities and its potential roles both as a pro-recombinase and as a suppressor of homologous recombination. Finally, the evidence for an emerging role in mitotic chromosome segregation is examined.

scholarly journals Pancreatic cancer in bloom syndrome

2019 ◽  
Vol 7 ◽  
pp. 2050313X1985558
Author(s):  
Itai Tzfoni ◽  
Jennifer Chayo ◽  
Meital Shaked ◽  
Ezra Bernstein ◽  
Roy Dekel ◽  
...  
Keyword(s):  
Pancreatic Cancer ◽  
Genomic Instability ◽  
Autosomal Recessive ◽  
Autosomal Recessive Disorder ◽  
Bloom Syndrome ◽  
Gastrointestinal Cancers ◽  
Recq Helicase ◽  
First Case ◽  
Physical Features ◽  
Blm Gene

Bloom syndrome is a rare autosomal recessive disorder characterized by distinct physical features, such as short stature, genomic instability, and predisposition to numerous cancers. The BLM gene encodes for the RecQ helicase that plays an important role in genome editing, maintenance, and stability. Mutations in the BLM gene cause genomic instability that exposes the carriers to a variety of cancers, and in particular hematological and gastrointestinal cancers. Herein, we report the first case of pancreatic cancer in a 32-year-old patient with bloom syndrome.

scholarly journals Bloom's syndrome protein response to ultraviolet-C radiation and hydroxyurea-mediated DNA synthesis inhibition

Oncogene ◽  
2002 ◽  
Vol 21 (13) ◽  
pp. 2079-2088 ◽  
Author(s):  
Mouna Ababou ◽  
Virginie Dumaire ◽  
Yann Lécluse ◽  
Mounira Amor-Guéret
Keyword(s):  
Dna Synthesis ◽  
Bloom's Syndrome ◽  
Synthesis Inhibition ◽  
Bloom’S Syndrome ◽  
Ultraviolet C ◽  
Protein Response ◽  
Syndrome Protein ◽  
Dna Synthesis Inhibition

Bloom’s syndrome protein unfolding G-quadruplexes in two pathways

2017 ◽  
Vol 26 (8) ◽  
pp. 088701
Author(s):  
Zhen-Ye Zhao ◽  
Chun-Hua Xu ◽  
Jing Shi ◽  
Jing-Hua Li ◽  
Jian-Bing Ma ◽  
...  
Keyword(s):  
Protein Unfolding ◽  
Bloom's Syndrome ◽  
Bloom’S Syndrome ◽  
Syndrome Protein

scholarly journals Stimulation of Flap Endonuclease-1 by the Bloom's Syndrome Protein

2003 ◽  
Vol 279 (11) ◽  
pp. 9847-9856 ◽  
Author(s):  
Sudha Sharma ◽  
Joshua A. Sommers ◽  
Leonard Wu ◽  
Vilhelm A. Bohr ◽  
Ian D. Hickson ◽  
...  
Keyword(s):  
Bloom's Syndrome ◽  
Flap Endonuclease 1 ◽  
Bloom’S Syndrome ◽  
Syndrome Protein ◽  
Stimulation Of

scholarly journals Phosphorylation of the Bloom's Syndrome Helicase and Its Role in Recovery from S-Phase Arrest

2004 ◽  
Vol 24 (3) ◽  
pp. 1279-1291 ◽  
Author(s):  
Sally L. Davies ◽  
Phillip S. North ◽  
Alwyn Dart ◽  
Nicholas D. Lakin ◽  
Ian D. Hickson
Keyword(s):  
Dna Replication ◽  
Genome Stability ◽  
Genetic Disorder ◽  
S Phase ◽  
Recq Helicase ◽  
Bloom's Syndrome ◽  
Recq Helicases ◽  
Phase Arrest ◽  
Bloom’S Syndrome ◽  
S Phase Arrest

ABSTRACT Bloom's syndrome (BS) is a human genetic disorder associated with cancer predisposition. The BS gene product, BLM, is a member of the RecQ helicase family, which is required for the maintenance of genome stability in all organisms. In budding and fission yeasts, loss of RecQ helicase function confers sensitivity to inhibitors of DNA replication, such as hydroxyurea (HU), by failure to execute normal cell cycle progression following recovery from such an S-phase arrest. We have examined the role of the human BLM protein in recovery from S-phase arrest mediated by HU and have probed whether the stress-activated ATR kinase, which functions in checkpoint signaling during S-phase arrest, plays a role in the regulation of BLM function. We show that, consistent with a role for BLM in protection of human cells against the toxicity associated with arrest of DNA replication, BS cells are hypersensitive to HU. BLM physically associates with ATR (ataxia telangiectasia and rad3+ related) protein and is phosphorylated on two residues in the N-terminal domain, Thr-99 and Thr-122, by this kinase. Moreover, BS cells ectopically expressing a BLM protein containing phosphorylation-resistant T99A/T122A substitutions fail to adequately recover from an HU-induced replication blockade, and the cells subsequently arrest at a caffeine-sensitive G2/M checkpoint. These abnormalities are not associated with a failure of the BLM-T99A/T122A protein to localize to replication foci or to colocalize either with ATR itself or with other proteins that are required for response to DNA damage, such as phosphorylated histone H2AX and RAD51. Our data indicate that RecQ helicases play a conserved role in recovery from perturbations in DNA replication and are consistent with a model in which RecQ helicases act to restore productive DNA replication following S-phase arrest and hence prevent subsequent genomic instability.

scholarly journals BLAP75, an essential component of Bloom's syndrome protein complexes that maintain genome integrity

2005 ◽  
Vol 24 (7) ◽  
pp. 1465-1476 ◽  
Author(s):  
Jinhu Yin ◽  
Alexandra Sobeck ◽  
Chang Xu ◽  
Amom Ruhikanta Meetei ◽  
Maureen Hoatlin ◽  
...  
Keyword(s):  
Protein Complexes ◽  
Genome Integrity ◽  
Bloom's Syndrome ◽  
Essential Component ◽  
Bloom’S Syndrome ◽  
Syndrome Protein
Sign in / Sign up

Export Citation Format

Share Document