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TeloRPA
Functions of the Replication Protein A (RPA) in telomere maintenance and genome stability, implication in pulmonary fibrosis and telomere diseases
FunderFrench National Research Agency (ANR)
Funder Contribution €595,676.00
DurationFrom 01 Jan 2021
Project codeANR-20-CE12-0012
Identifiers
Description
Telomeres are short tandemly repeated DNA sequences at the end of chromosomes that preserve genome stability. Abnormal telomere shortening causes telomere syndrome, a rare monogenic disease characterized by bone marrow failure Dyskeratosis Congenita, aplastic anemia and idiopathic pulmonary fibrosis (IPF). Strikingly, rare heterozygous variations predicted to be deleterious in genes encoding for the subunits of RPA genes were identified in patients with short telomeres developing IPF. RPA is a heterotrimeric ssDNA binding protein involved in DNA replication, recombination and repair. Our preliminary results show that RPA patient variations provoke telomeric defects in cells harboring these mutations. These data strengthen our hypothesis that RPA is required to maintain repeated telomeric sequences in human. Our objective is to investigate the role of RPA at telomeres through the characterization of several RPA mutations and to validate RPA genes as genetic factor for telomere diseases.
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Telomeres are short tandemly repeated DNA sequences at the end of chromosomes that preserve genome stability. Abnormal telomere shortening causes telomere syndrome, a rare monogenic disease characterized by bone marrow failure Dyskeratosis Congenita, aplastic anemia and idiopathic pulmonary fibrosis (IPF). Strikingly, rare heterozygous variations predicted to be deleterious in genes encoding for the subunits of RPA genes were identified in patients with short telomeres developing IPF. RPA is a heterotrimeric ssDNA binding protein involved in DNA replication, recombination and repair. Our preliminary results show that RPA patient variations provoke telomeric defects in cells harboring these mutations. These data strengthen our hypothesis that RPA is required to maintain repeated telomeric sequences in human. Our objective is to investigate the role of RPA at telomeres through the characterization of several RPA mutations and to validate RPA genes as genetic factor for telomere diseases.
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