In which phase of the cell cycle are cells likely to accumulate DNA damage if they do not enter M phase?

Cells are most likely to accumulate DNA damage if they do not enter M phase during the G2 phase. G2 is the phase that follows DNA replication in S phase and precedes mitosis (M phase). During G2, the cell is preparing for mitosis, and it undergoes a series of checks to ensure that the DNA has been replicated correctly and is undamaged.

If the cell has sustained DNA damage and does not complete the necessary repairs, it may lead to problems during mitosis, such as chromosomal instability. Typically, the G2/M checkpoint serves as a safeguard, delaying entry into mitosis until all damage has been repaired. However, if the cell remains in G2 without entering M phase, it may accumulate more damage over time, especially as it is still metabolically active and potentially exposed to factors that can further harm the DNA.

In contrast, G1 is primarily focused on cell growth and preparing for DNA replication, the S phase is where DNA synthesis occurs, and in M phase, cells are actively dividing. While damage can occur in any phase, the context of remaining stuck in G2 emphasizes the heightened risk of accumulating DNA damage without progressing to mitosis, where any attempted repair and assessment would typically occur.