This report describes ataxia-telangiectasia-like disorder 1, an autosomal recessive disorder characterized by progressive cerebellar degeneration resulting in ataxia and oculomotor apraxia. The human gene implicated is MRE11, which encodes a nuclear protein involved in homologous recombination, telomere length maintenance, and DNA double-strand break repair. There is one high-scoring fly ortholog, Dmel\mre11, for which multiple genetic reagents, including an amorphic allele, RNAi-targeting constructs, and alleles caused by insertional mutagenesis have been generated.
Human MRE11 has not been introduced into flies.
Mushroom body-specific RNAi knockdown of Dmel\mre11 affects both startle-induced and spontaneous motor behavior, and also results in an increase in apoptosis in Kenyon cells.
[updated Jun. 2024 by FlyBase; FBrf0222196]
Autosomal recessive cerebellar ataxias (ARCA) are a heterogeneous group of rare neurological disorders involving both central and peripheral nervous system, and in some case other systems and organs, and characterized by degeneration or abnormal development of cerebellum and spinal cord, autosomal recessive inheritance and, in most cases, early onset occurring before the age of 20 years (Palau and Espinos, 2006; pubmed:17112370).
The hereditary ataxias are a group of genetic disorders characterized by slowly progressive incoordination of gait and often associated with poor coordination of hands, speech, and eye movements. Frequently, atrophy of the cerebellum occurs. [from Gene Reviews, Hereditary Ataxia Overview; pubmed:20301317; 2017.06.16]
See also Jayadev and Bird, 2013 (pubmed:23538602).
Autosomal recessive spinocerebellar ataxia is a neurologic disorder characterized by onset of progressive gait difficulties, eye movement abnormalities, and dysarthria in the first or second decade of life (summary, Dy et al, 2105; pubmed:26224725). [from MIM:609270; 2020.07.13]
[ATAXIA-TELANGIECTASIA-LIKE DISORDER 1; ATLD1](https://omim.org/entry/604391)
[MRE11 HOMOLOG, DOUBLE-STRAND BREAK REPAIR NUCLEASE; MRE11](https://omim.org/entry/600814)
Ataxia-telangiectasia-like disorder-1 is an autosomal recessive disorder characterized clinically by progressive cerebellar degeneration resulting in ataxia and oculomotor apraxia. Laboratory studies of patient cells showed increased susceptibility to radiation, consistent with a defect in DNA repair. The disorder shares some phenotypic features of ataxia-telangiectasia (MIM:208900; FBhh0000167), but telangiectases and immune deficiency are not present in ATLD1 (summary by Hernandez et al., 1993, pubmed:8445618 and Stewart et al., 1999, pubmed:10612394). [from MIM:604391; 2024.06.05]
Ataxia-telangiectasia-like disorder-1 (ATLD1) is caused by homozygous or compound heterozygous mutation in the MRE11 gene on chromosome 11q21. [from MIM:604391; 2024.06.05]
MRE11 encodes a nuclear protein involved in homologous recombination, telomere length maintenance, and DNA double-strand break repair. By itself, the protein has 3' to 5' exonuclease activity and endonuclease activity. The protein forms a complex with the RAD50 homolog; this complex is required for nonhomologous joining of DNA ends and possesses increased single-stranded DNA endonuclease and 3' to 5' exonuclease activities. In conjunction with a DNA ligase, this protein promotes the joining of noncomplementary ends in vitro using short homologies near the ends of the DNA fragments. [provided by RefSeq, Jul 2008]
One to one (1 human to 1 Drosophila); MRE11 has one high-scoring Drosophila ortholog, mre11.
High-scoring ortholog of human MRE11 (1 Drosophila to 1 human).
