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Steps of the cell cycle. The G 2-M checkpoint occurs between the G 2 and M phases. G2-M arrest. The G 2-M DNA damage checkpoint is an important cell cycle checkpoint in eukaryotic organisms that ensures that cells don't initiate mitosis until damaged or incompletely replicated DNA is sufficiently repaired.
When there is too much damage, apoptosis is triggered in order to protect the organism from potentially harmful cells.7 p53, also known as a tumor suppressor gene, is a major regulatory protein in the DNA damage response system which binds directly to the promoters of its target genes. p53 acts primarily at the G1 checkpoint (controlling the G1 ...
Similar to S Phase, G2 experiences a DNA damage checkpoint. The cell is once more examined for sites of DNA damage or incomplete replication, and the kinases ATR and ATM are recruited to damage sites. Activation of Chk1 and Chk2 also transpire, as well as p53 activation, to induce cell cycle arrest and halt progression into mitosis.
DNA damage checkpoint is a signal transduction pathway that blocks cell cycle progression in G1, G2 and metaphase and slows down the rate of S phase progression when DNA is damaged. It leads to a pause in cell cycle allowing the cell time to repair the damage before continuing to divide.
DNA damage induces the activation of Chk1 which facilitates the initiation of the DNA damage response (DDR) and cell cycle checkpoints. The DNA damage response is a network of signaling pathways that leads to activation of checkpoints, DNA repair and apoptosis to inhibit damaged cells from progressing through the cell cycle.
Of the four DNA damage checkpoints, two have an additional process for monitoring DNA damage other than activating p53. Before entry into S phase and during S phase, ATM/R also activates Chk1/2 that inhibits Cdc25A, a protein responsible for activating cyclin-Cdk dimers. Without cyclin dimer activation, the cell cannot transition through the cycle.
Detection of DNA damage induces activation of three canonical S-phase "checkpoint pathways" that delay or arrest further cell cycle progression: [12] The Replication Checkpoint detects stalled replication forks by integrating signals from RPA, ATR Interacting Protein (ATRIP), and RAD17. [12]
CHEK2 (Checkpoint kinase 2) is a tumor suppressor gene that encodes the protein CHK2, a serine-threonine kinase. CHK2 is involved in DNA repair, cell cycle arrest or apoptosis in response to DNA damage. Mutations to the CHEK2 gene have been linked to a wide range of cancers. [5]