Question

S-phase arrest in response to glutamine deprivation in KRas-driven cancer cells can be reversed by aspartate.

true or false

Answer 1

This statement is true

S-phase arrest in response to glutamine deprivation in KRas-driven cancer cells can be reversed by aspartate.

Explanation:

The cell requires glutamine ( essential amino acid ) during the cell cycle to use as a carbon source in the tricarboxylic acid cycle and also use as a nitrogen source for the synthesis of the nucleotides. The normal cells arrest in the G1 phase of the cell cycle if it gets deprived of the glutamine but the KRas-driven cancer cells arrest in the S phase because of the deprivation of the glutamine which leads to the unavailability deoxynucleotides for the synthesis of the DNA. Due to the lack of the deoxynucleotides the cell undergoes replicative stress which activates the ATR and Chk1-mediated proteins that cause S-phase arrest in the KRas-driven cancer cells.

In the normal cell during cell cycle the glutamine converts into glutamate by deamidation and then glutamate into α-ketoglutarate (α-KG) by deamination, this α-ketoglutarate (α-KG) serves the intermediate of the tricarboxylic acid cycle. But in the KRas-driven cancer cells during the glutamate transformation into alpha-ketoglutarate the transformation of the oxaloacetate to aspartate also occurs by a reaction called transamination and the GOT2 enzyme (Glutamic-Oxaloacetic Transaminase 2 ) catalyze this reaction. This aspartate is very important for deoxynucleotide biosynthesis during the cell dividing phase and it helps in the reversion of the S phase arrest in the KRas-driven cancer cells.