RFC1

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Proteine

title: "RFC1" type: doc version: 1 created: 2026-02-28 author: "Wikipedia contributors" status: active scope: public description: "Proteine" topic_path: "uncategorized" source: "https://en.wikipedia.org/wiki/RFC1" license: "CC BY-SA 4.0" wikipedia_page_id: 0 wikipedia_revision_id: 0

::summary Proteine ::

Replication factor C subunit 1 is a protein that in humans is encoded by the RFC1 gene.

Function

The protein encoded by this gene is the large subunit of replication factor C, which is a five subunit DNA polymerase accessory protein. Replication factor C is a DNA-dependent ATPase that is required for eukaryotic DNA replication and repair. The protein acts as an activator of DNA polymerases, binds to the 3' end of primers, and promotes coordinated synthesis of both strands. It also may have a role in telomere stability.

Interactions

RFC1 has been shown to interact with:

Clinical relevance

Biallelic intronic repeat expansions (a series of repeating nucleotide sequences) in the replication factor C subunit 1 (RFC1) gene causes cerebellar ataxia, neuropathy and vestibular areflexia syndrome (CANVAS). Within the poly(A) tail of an AluSx3 element in RFC1, there are eleven repeats of the pentanucleotide "AAAAG". Repeat expansion and polymorphic configuration are observed in part of the population, with increased number of repeats associated to alternative "AAAGG", "AAGGG" and "ACAGG" pentanucleotides. In particular, biallelic "AAGGG" and "ACAGG" repeat expansion have disproportionately been observed in patients with CANVAS. Biallelic "AAGGG" repeat expansion is also reported in a high number of sporadic cases of late-onset ataxia, isolate sensory neuropathy and, less frequently, isolate cerebellar ataxia. Due to a diagnostic overlap with CANVAS, researchers have also investigated the presence of RFC1 expansions in pathologically confirmed multiple system atrophy (MSA) but found a similar alteration frequency (0.7%) to a healthy population, suggesting RFC1 does not have a role in this disease.

Mutant biallelic intronic repeat expansions do not affect RFC1 expression in patient peripheral and brain tissue, suggesting no overt loss of function of this gene.

In patients with the pathogenic RFC1 expansion, sensory neuropathy appears to be a predominant feature and patients may also present with symptoms such as cerebellar dysfunction, vestibular involvement and a dry spasmodic cough therefore, genetic testing is recommended in those with these symptoms.

References

References

  1. (March 1994). "Cloning, expression, and chromosomal localization of the 140-kilodalton subunit of replication factor C from mice and humans". Molecular and Cellular Biology.
  2. "Entrez Gene: ''RFC1'' replication factor C (activator 1) 1, 145kDa".
  3. (September 2002). "A Mammalian bromodomain protein, brd4, interacts with replication factor C and inhibits progression to S phase". Molecular and Cellular Biology.
  4. (August 2002). "The large subunit of replication factor C interacts with the histone deacetylase, HDAC1". The Journal of Biological Chemistry.
  5. (August 1996). "A conserved domain of the large subunit of replication factor C binds PCNA and acts like a dominant negative inhibitor of DNA replication in mammalian cells". The EMBO Journal.
  6. (January 1997). "Replication factor C interacts with the C-terminal side of proliferating cell nuclear antigen". The Journal of Biological Chemistry.
  7. (April 1999). "The DNA-binding subunit p140 of replication factor C is upregulated in cycling cells and associates with G1 phase cell cycle regulatory proteins". Journal of Molecular Medicine.
  8. (October 2002). "A proteomics approach to identify proliferating cell nuclear antigen (PCNA)-binding proteins in human cell lysates. Identification of the human CHL12/RFCs2-5 complex as a novel PCNA-binding protein". The Journal of Biological Chemistry.
  9. (January 2003). "Regulation of RelA (p65) function by the large subunit of replication factor C". Molecular and Cellular Biology.
  10. (March 1998). "Reconstitution of recombinant human replication factor C (RFC) and identification of an RFC subcomplex possessing DNA-dependent ATPase activity". The Journal of Biological Chemistry.
  11. (June 1996). "In vitro reconstitution of human replication factor C from its five subunits". Proceedings of the National Academy of Sciences of the United States of America.
  12. (April 2008). "DNA damage-induced ubiquitylation of RFC2 subunit of replication factor C complex". The Journal of Biological Chemistry.
  13. (May 2019). "Author Correction: Biallelic expansion of an intronic repeat in ''RFC1'' is a common cause of late-onset ataxia". Nature Genetics.
  14. (October 2020). "A novel ''RFC1'' repeat motif (ACAGG) in two Asia-Pacific CANVAS families". Brain.
  15. (April 2021). "''RFC1'' AAGGG repeat expansion masquerading as Chronic Idiopathic Axonal Polyneuropathy". Journal of Neurology.
  16. (June 2021). "''RFC1'' expansions are a common cause of idiopathic sensory neuropathy". Brain.
  17. (March 2021). "Natural History, Phenotypic Spectrum, and Discriminative Features of Multisystemic ''RFC1''-disease". Neurology.
  18. (April 2020). "''RFC1'' Intronic Repeat Expansions Absent in Pathologically Confirmed Multiple Systems Atrophy". Movement Disorders.
  19. (February 2020). "Cerebellar ataxia, neuropathy, vestibular areflexia syndrome due to ''RFC1'' repeat expansion". Brain.

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