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中文摘要
翻译
WRN基因突变的患者会发展为沃纳综合征(WS),这是一种早衰疾病。一般来说,WS细胞具有高度的基因组不稳定性,DNA缺失、插入和重排的数量增加。这些影响可能是DNA修复、复制和/或重组缺陷的潜在结果,尽管实际的生化缺陷尚不清楚。
英文摘要
Patients with mutations in the WRN gene develop Werner syndrome (WS), a premature aging disorder. In general, WS cells have a high level of genomic instability, with increased amounts of DNA deletions, insertions, and rearrangements. These effects could potentially be the result of defects in DNA repair, replication, and/or recombination, although the actual biochemical defect remains unclear. In addition to being a premature aging disorder, WS patients develop a unique set of cancers and therefore studying WS affords us an opportunity to investigate the relationship between cancer and aging. Notably, aging is the greatest risk fact for cancer and involves senescence and the loss of function of tissues. We, and others, have shown that loss of Wrn impacts the epigenome and epigenetic changes are common in aging. How WRN protein contributes to cancer and aging in various tissues is under investigation. WRN protein possesses both helicase and exonuclease functions. Our laboratory investigates the localization of WRN to sites of DNA damage using confocal microscopy coupled with site directed mutagenesis of critical amino acids in WRN protein. Our findings show that basic residues are important for its localization and that amino acids modified by posttranslational modifications can modulate WRNs re-localization to sites of DNA and its retention times there.
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Mitochondrial DNA Repair Processes In Oxidative Stress And Aging
  • 批准号:
    10471691
  • 项目类别:
  • 资助金额:
    $62.25万
  • 财政年份:
    --
  • 负责人:
    Vilhelm A Bohr
  • 依托单位:
OXIDATIVE DNA DAMAGE AND ITS PROCESSING
  • 批准号:
    6431453
  • 项目类别:
  • 资助金额:
    $0.0万
  • 财政年份:
    --
  • 负责人:
    Vilhelm A Bohr
  • 依托单位:
GENOMIC INSTABILITY
  • 批准号:
    6431454
  • 项目类别:
  • 资助金额:
    $0.0万
  • 财政年份:
    --
  • 负责人:
    Vilhelm A Bohr
  • 依托单位:
Oxidative Dna Damage And Its Processing
  • 批准号:
    6530362
  • 项目类别:
  • 资助金额:
    $0.0万
  • 财政年份:
    --
  • 负责人:
    Vilhelm A Bohr
  • 依托单位:
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