How does alkylating agents cause DNA damage?

How does alkylating agents cause DNA damage?

Alkylating agents prevent cell division primarily by cross-linking strands of DNA. Because of continued synthesis of other cell constituents, such as RNA and protein, growth is unbalanced, and the cell dies.

Do alkylating agents interfere with DNA repair?

“Alkylating agents act directly on DNA, causing cross-linking of DNA strands, abnormal base pairing, or DNA strand breaks, thus preventing the cell from dividing.

What are the DNA repair pathways that repair damaged DNA bases?

At least five major DNA repair pathways—base excision repair (BER), nucleotide excision repair (NER), mismatch repair (MMR), homologous recombination (HR) and non-homologous end joining (NHEJ)—are active throughout different stages of the cell cycle, allowing the cells to repair the DNA damage.

What is DNA damage response pathway?

The DNA damage response (DDR) comprises a set of signaling pathways for the detection and repair of DNA damage and includes the MMR system for mispaired bases, the base excision repair system for small base modifications, the nucleotide excision repair for intrastrand crosslinks and pyrimidine dimers, the single-strand …

What is DNA damage?

DNA damage is defined as an alteration in DNA structure that is capable of causing cellular injury and reduces viability or reproductive fitness of the organism (Kaufmann and Paules, 1996).

How do alkylating agents induce mutations?

Mutagenicity is related to the ability of alkylating agents to form crosslinks and/or transfer an alkyl group to form monoadducts in DNA. The most frequent location of adducts in the DNA is at guanines. Expressed mutations involve different base substitutions, including all types of transitions and transversions.

What causes DNA damage?

DNA damage occurs continuously as a result of various factors—intracellular metabolism, replication, and exposure to genotoxic agents, such as ionizing radiation and chemotherapy. If left unrepaired, this damage could result in changes or mutations within the cell genomic material.

What is one of the main effects of DNA damage?

DNA damage can affect normal cell replicative function and impact rates of apoptosis (programmed cell death, often referred to as ‘cellular senescence’). Alternatively, damage to genetic material can result in impaired cellular function, cell loss, or the transformation of healthy cells to cancers.

How does DNA damage impact health and life?

DNA damage contributes to aging via cell autonomous events such as causing apoptosis, which depletes functional cells such as neurons, and via cell non-autonomous mechanisms such as triggering senescence, which can negatively impact the function of neighboring, undamaged cells through their SASP.

What type of DNA damage does Nitrosoguanidine cause?

MNNG has been used to induce DNA methylation damage that is directly recognized by MMR proteins (10, 23), which results in recruitment of MMR proteins to the nucleus (32, 33).