Bloom's syndrome: Why not premature aging?: A comparison of the BLM and WRN helicases

Christelle de Renty, Nathan Ellis

Research output: Contribution to journalReview article

18 Citations (Scopus)

Abstract

Genomic instability is a hallmark of cancer and aging. Premature aging (progeroid) syndromes are often caused by mutations in genes whose function is to ensure genomic integrity. The RecQ family of DNA helicases is highly conserved and plays crucial roles as genome caretakers. In humans, mutations in three RecQ genes — BLM, WRN, and RECQL4 — give rise to Bloom's syndrome (BS), Werner syndrome (WS), and Rothmund-Thomson syndrome (RTS), respectively. WS is a prototypic premature aging disorder; however, the clinical features present in BS and RTS do not indicate accelerated aging. The BLM helicase has pivotal functions at the crossroads of DNA replication, recombination, and repair. BS cells exhibit a characteristic form of genomic instability that includes excessive homologous recombination. The excessive homologous recombination drives the development in BS of the many types of cancers that affect persons in the normal population. Replication delay and slower cell turnover rates have been proposed to explain many features of BS, such as short stature. More recently, aberrant transcriptional regulation of growth and survival genes has been proposed as a hypothesis to explain features of BS.

Original languageEnglish (US)
Pages (from-to)36-51
Number of pages16
JournalAgeing Research Reviews
Volume33
DOIs
StatePublished - Jan 1 2017

Fingerprint

Bloom Syndrome
Premature Aging
Genes
Aging of materials
Rothmund-Thomson Syndrome
Werner Syndrome
RecQ Helicases
Genomic Instability
Homologous Recombination
Recombinational DNA Repair
Mutation
Repair
DNA Replication
DNA Repair
DNA
Neoplasms
Genome
Survival
Growth
Population

Keywords

  • Aging
  • BLM
  • Bloom's syndrome
  • Cancer susceptibility
  • Genomic instability
  • RecQ helicases

ASJC Scopus subject areas

  • Biotechnology
  • Biochemistry
  • Aging
  • Molecular Biology
  • Neurology

Cite this

Bloom's syndrome : Why not premature aging?: A comparison of the BLM and WRN helicases. / de Renty, Christelle; Ellis, Nathan.

In: Ageing Research Reviews, Vol. 33, 01.01.2017, p. 36-51.

Research output: Contribution to journalReview article

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AB - Genomic instability is a hallmark of cancer and aging. Premature aging (progeroid) syndromes are often caused by mutations in genes whose function is to ensure genomic integrity. The RecQ family of DNA helicases is highly conserved and plays crucial roles as genome caretakers. In humans, mutations in three RecQ genes — BLM, WRN, and RECQL4 — give rise to Bloom's syndrome (BS), Werner syndrome (WS), and Rothmund-Thomson syndrome (RTS), respectively. WS is a prototypic premature aging disorder; however, the clinical features present in BS and RTS do not indicate accelerated aging. The BLM helicase has pivotal functions at the crossroads of DNA replication, recombination, and repair. BS cells exhibit a characteristic form of genomic instability that includes excessive homologous recombination. The excessive homologous recombination drives the development in BS of the many types of cancers that affect persons in the normal population. Replication delay and slower cell turnover rates have been proposed to explain many features of BS, such as short stature. More recently, aberrant transcriptional regulation of growth and survival genes has been proposed as a hypothesis to explain features of BS.

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