DNA end resection
[1]Double-strand breaks (DSBs) can occur at any phase of the cell cycle causing DNA end resection and repair activities to take place, but they are also normal intermediates in mitosis recombination.
[3] NHEJ mechanism functions in ligating two different DSBs with high fidelity, while HR relies on a homologous template to repair DSB ends.
[4][3] Since HR pathway requires sister chromatids for activation, this event only happens in the G2 and S phases of the cell cycle during replication.
[16] Linear chromosomes are packed into complex specialized DNA protective packages called telomeres.
[3][4] The structure of telomeres is highly conserve and is organized in multiple short tandem DNA repeats.
[3] During telomeric DNA replication in the S/G2 and G1 phases of the cell cycle, the 3' lagging strand leaves a short overhang called a G-tail.
[4] In the G1 phase of the cell cycle, the telomere-associated proteins RIF1, RIF2, and RAP2 bind to telomeric DNA and prevent access to the MRX complex.
[3] This results in an inhibition of telomerase elongation at the DSB ends and prevents further telomere action at the G1 phase of the cell cycle.
[3][4] In the late S/G2 phase of the cell cycle, the telomere-associated proteins RIF1, RIF2, and RAP2 exhibit their inhibitory effect by binding to telomeric DNA.
[3] One of the important regulatory controls in mitotic cells is deciding which specific DSB repair pathway to take.
[4][3] After phosphorylation occurs by Cdk1, MRX complex binds to dsDNA ends and generates short ssDNA that stretches in the 5' direction.
The resulting phosphorylation by Sae2 by Mec1 helps increase the effect of resection and this in turn leads to the DNA damage checkpoint activation.
[4][3] The pathway of choice in DNA repair is highly regulated to guarantee that cells in the S/G2 and G1 phase use the appropriate mechanism.
For NHEJ pathway to occur, positive regulators such as the Ku and MRX complex mediate recruitment of other NHEJ-associated proteins such as Tel1, Lif1, Dnl4, and Nej1.
