The FA (Fanconi anaemia) FANCD2 protein is pivotal in the cellular response to DNA interstrand cross-links. Establishing cells expressing exogenous FANCD2 has proven to be difficult compared with other DNA repair genes. We find that in transformed normal human fibroblasts, exogenous nuclear expression of FANCD2 induces apoptosis, dependent specifically on exons 10-13. This is the same region required for interaction with the histone acetyltransferase, Tip60. Deletion of exons 10-13 from FANCD2 N-terminal constructs (nucleotides 1-1100) eliminates the binary interaction with Tip60 and the cellular apoptotic response; moreover, cells can stably express FANCD2 at high levels if Tip60 is depleted. The results indicate that FANCD2-sponsored apoptosis requires an interaction with Tip60 and depends on Tip60.
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http://dx.doi.org/10.1042/CBI20090251 | DOI Listing |
Hum Genomics
September 2024
The Second School of Medicine, Guangxi Medical University, No. 166, Daxuedong Road, Xixiangtang District, Nanning, Guangxi Zhuang Autonomous Region, 530007, China.
Hum Gene Ther
February 2024
Department of Neurology, University of California Davis, School of Medicine, Sacramento, California, USA.
The enzyme choline acetyltransferase (ChAT) synthesizes acetylcholine from acetyl-CoA and choline at the neuromuscular junction and at the nerve terminals of cholinergic neurons. Mutations in the ChAT gene () result in a presynaptic congenital myasthenic syndrome (CMS) that often associates with life-threatening episodes of apnea. Knockout mice for die at birth.
View Article and Find Full Text PDFAnn Hum Genet
November 2022
Bachir Mentouri Public Hospital, Academic General Surgery Services, School of Medicine, University of Algiers-1, Kouba, Algeria.
Colorectal cancer is the second leading cause of cancer-related deaths in women and men in Algeria. Lynch syndrome (LS) is an autosomal dominant disease caused by heterozygous germline pathogenic variants in mismatch repair genes (MMR) and frequently predisposes to colorectal cancer. However, data about MMR germline pathogenic variants in Algerian patients are limited.
View Article and Find Full Text PDFMol Genet Metab Rep
June 2022
Department of Human Genetics, National Children's Hospital, Hanoi, Viet Nam.
Background: Wilson disease (WD) is caused by mutations in the copper-transporting P-type adenosine triphosphatase encoded by the gene. In this study, we screened and identified the mutations among unrelated Vietnamese pediatric patients.
Methods: One-hundred-thirteen pediatric patients with clinically diagnosed WD were recruited.
BMC Genomics
June 2022
FRIGE's Institute of Human Genetics, FRIGE House, Jodhpur Village Road, Satellite, Ahmedabad, Gujarat, 380015, India.
Background: Mucopolysaccharidosis IVA (Morquio syndrome A, MPS IVA) is an autosomal recessive lysosomal storage disorder caused due to biallelic variants in the N-acetylgalactoseamine-6-sulfate sulfatase (GALNS) gene. The mutation spectrum in this condition is determined amongst sub-populations belonging to the north, south and east India geography, however, sub-populations of west Indian origin, especially Gujarati-Indians, are yet to be studied. We aimed to analyse the variants present in the GLANS gene amongst the population of Gujarat by sequencing all exons and exon-intron boundaries of the GALNS gene in patients from 23 unrelated families.
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