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Dna damage response

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Cell Biology

Definition

DNA damage response (DDR) refers to the set of cellular processes that detect and repair damaged DNA to maintain genomic stability. This mechanism is crucial for preventing mutations that could lead to cell death or diseases like cancer, and it intricately connects with cellular decisions related to survival and apoptosis.

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5 Must Know Facts For Your Next Test

  1. The DNA damage response involves various proteins and pathways, including ATM and ATR kinases, which activate repair processes or initiate apoptosis if the damage is irreparable.
  2. DDR is critical for maintaining genomic integrity, as failure in this response can lead to genomic instability and contribute to the development of cancer.
  3. Cells utilize different pathways within the DDR depending on the type of damage; for instance, single-strand breaks are often repaired via base excision repair, while double-strand breaks may utilize non-homologous end joining or homologous recombination.
  4. The p53 protein plays a pivotal role in the DDR by acting as a tumor suppressor that can induce cell cycle arrest or apoptosis in response to significant DNA damage.
  5. The efficiency of the DNA damage response can be influenced by various factors, including cellular stressors like radiation, chemicals, and oxidative stress, which can increase the likelihood of DNA lesions.

Review Questions

  • How does the DNA damage response influence cellular decisions regarding survival and apoptosis?
    • The DNA damage response is crucial in determining whether a cell will survive or undergo apoptosis when faced with significant DNA damage. When the DDR detects DNA lesions, it activates pathways that can either repair the damage or signal for programmed cell death if the damage is beyond repair. This decision-making process helps prevent the propagation of mutated cells that could lead to cancer, maintaining overall genomic stability.
  • Discuss the role of checkpoint kinases in the DNA damage response and their impact on cell cycle regulation.
    • Checkpoint kinases such as ATM and ATR are essential components of the DNA damage response that help regulate the cell cycle. When DNA damage is detected, these kinases activate checkpoints that temporarily halt cell cycle progression, allowing time for repair mechanisms to fix any issues before division occurs. This regulatory function is critical for preventing cells from replicating damaged DNA, which could lead to harmful mutations.
  • Evaluate how defects in the DNA damage response mechanisms contribute to cancer development and progression.
    • Defects in the DNA damage response mechanisms can significantly contribute to cancer development by allowing cells with damaged DNA to evade repair processes and continue dividing. For instance, mutations in key DDR proteins like p53 can lead to impaired apoptosis and unchecked cellular proliferation. As a result, this can promote genomic instability, increase mutation rates, and ultimately facilitate cancer progression through clonal expansion of aberrant cells.

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