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

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• 作者：Christelle de Renty ; Nathan A. Ellis ; ^{naellis@email.arizona.edu}
• 关键词：Bloom&rsquo ; s syndrome ; RecQ helicases ; BLM ; Genomic instability ; Cancer susceptibility ; Aging
• 刊名：Ageing Research Reviews
• 出版年：2017
• 出版时间：January 2017
• 年：2017
• 卷：33
• 期：Complete
• 页码：36-51
• 全文大小：2802 K
• 卷排序：33

文摘

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.