cellular response to hydroxyurea

Definition

Target type: biologicalprocess

Any process that results in a change in state or activity of a cell (in terms of movement, secretion, enzyme production, gene expression, etc.) as a result of a hydroxyurea stimulus. [GOC:mah]

Hydroxyurea (HU) is a ribonucleotide reductase inhibitor that exerts its effects by interfering with DNA synthesis. Upon entering the cell, HU is taken up by the enzyme ribonucleotide reductase (RNR), a key enzyme in the de novo synthesis of deoxyribonucleotides (dNTPs) which are the building blocks of DNA. HU binds to the active site of RNR, inhibiting the conversion of ribonucleotides to deoxyribonucleotides. This inhibition leads to a depletion of dNTPs, ultimately halting DNA replication and cell cycle progression.

The cellular response to HU is multifaceted and involves several pathways.

1. **Cell Cycle Arrest:** The depletion of dNTPs triggers a checkpoint response, halting the cell cycle at the S phase, the phase where DNA replication occurs. This arrest provides time for DNA repair mechanisms to function.

2. **DNA Damage Response:** HU-induced depletion of dNTPs can lead to stalled replication forks. These stalled forks activate the DNA damage response (DDR) pathway. This intricate network of proteins recognizes and repairs DNA damage.

3. **Apoptosis:** If the DNA damage is too severe or if repair mechanisms are overwhelmed, the cell may initiate apoptosis, a programmed cell death pathway. Apoptosis eliminates damaged cells from the population.

4. **Adaptive Response:** Some cells, particularly cancer cells, can develop resistance to HU. This resistance may arise through several mechanisms, including mutations in RNR, increased expression of DNA repair proteins, or upregulation of alternative pathways for dNTP synthesis.

Overall, the cellular response to HU is a complex interplay of various pathways aimed at minimizing DNA damage and maintaining genomic integrity. The ultimate outcome depends on the cellular context, the duration of exposure, and the cell's ability to repair DNA damage.'
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Proteins (2)

Compounds (6)