Structure of the RecQ C-terminal domain of human Bloom syndrome protein.

[werner syndrome]

Bloom syndrome is a rare genetic disorder characterized by genomic instability and cancer predisposition . The disease is caused by mutations of the Bloom syndrome protein (BLM ). Here we report the crystal structure of a RecQ C-terminal (RQC ) domain from human BLM . The structure reveals three novel features of BLM RQC which distinguish it from the previous structures of the Werner syndrome protein (WRN ) and RECQ 1 . First , BLM RQC lacks an aromatic residue at the tip of the β-wing , a key element of the RecQ-family helicases used for DNA-strand separation . Second , a BLM -specific insertion between the N-terminal helices exhibits a looping-out structure that extends at right angles to the β-wing . Deletion mutagenesis of this insertion interfered with binding to Holliday junction . Third , the C-terminal region of BLM RQC adopts an extended structure running along the domain surface , which may facilitate the spatial positioning of an HRDC domain in the full-length protein .

Diseases
Validation

Diseases presenting "cancer" symptom

achondroplasia

acute rheumatic fever

adrenal incidentaloma

alpha-thalassemia

benign recurrent intrahepatic cholestasis

cadasil

canavan disease

carcinoma of the gallbladder

cholangiocarcinoma

coats disease

congenital adrenal hyperplasia

congenital diaphragmatic hernia

cowden syndrome

cushing syndrome

cutaneous mastocytosis

dedifferentiated liposarcoma

dystrophic epidermolysis bullosa

epidermolysis bullosa simplex

erdheim-chester disease

erythropoietic protoporphyria

esophageal adenocarcinoma

esophageal carcinoma

esophageal squamous cell carcinoma

familial hypocalciuric hypercalcemia

familial mediterranean fever

gm1 gangliosidosis

heparin-induced thrombocytopenia

hereditary cerebral hemorrhage with amyloidosis

hirschsprung disease

hodgkin lymphoma, classical

inclusion body myositis

junctional epidermolysis bullosa

kabuki syndrome

kallmann syndrome

kindler syndrome

lamellar ichthyosis

liposarcoma

locked-in syndrome

lymphangioleiomyomatosis

monosomy 21

neuralgic amyotrophy

oculocutaneous albinism

oligodontia

oral submucous fibrosis

papillon-lefèvre syndrome

pendred syndrome

pleomorphic liposarcoma

primary effusion lymphoma

proteus syndrome

pyomyositis

pyruvate dehydrogenase deficiency

severe combined immunodeficiency

sneddon syndrome

systemic capillary leak syndrome

triple a syndrome

von hippel-lindau disease

waldenström macroglobulinemia

well-differentiated liposarcoma

werner syndrome

wiskott-aldrich syndrome

wolf-hirschhorn syndrome

x-linked adrenoleukodystrophy

This symptom has already been validated