Acetylation of Werner syndrome protein (WRN): relationships with DNA damage, DNA replication and DNA metabolic activities.

[werner syndrome]

Loss of Werner syndrome protein function causes Werner syndrome , characterized by increased genomic instability , elevated cancer susceptibility and premature aging . Although WRN is subject to acetylation , phosphorylation and sumoylation , the impact of these modifications on WRN 's DNA metabolic function remains unclear . Here , we examined in further depth the relationship between WRN acetylation and its role in DNA metabolism , particularly in response to induced DNA damage . Our results demonstrate that endogenous WRN is acetylated somewhat under unperturbed conditions . However , levels of acetylated WRN significantly increase after treatment with certain DNA damaging agents or the replication inhibitor HU . Use of DNA repair-deficient cells or repair pathway inhibitors further increase levels of acetylated WRN , indicating that induced DNA lesions and their persistence are at least partly responsible for increased acetylation . Notably , acetylation of WRN correlates with inhibition of DNA synthesis , suggesting that replication blockage might underlie this effect . Moreover , WRN acetylation modulates its affinity for and activity on certain DNA structures , in a manner that may enhance its relative specificity for physiological substrates . Our results also show that acetylation and deacetylation of endogenous WRN is a dynamic process , with sirtuins and other histone deacetylases contributing to WRN deacetylation . These findings advance our understanding of the dynamics of WRN acetylation under unperturbed conditions and following DNA damage induction , linking this modification not only to DNA damage persistence but also potentially to replication stalling caused by specific DNA lesions . Our results are consistent with proposed metabolic roles for WRN and genomic instability phenotypes associated with WRN deficiency .

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