Search results
Results from the WOW.Com Content Network
Eukaryotic cells exposed to DNA damaging agents also activate important defensive pathways by inducing multiple proteins involved in DNA repair, cell cycle checkpoint control, protein trafficking and degradation. Such genome wide transcriptional response is very complex and tightly regulated, thus allowing coordinated global response to damage.
Inefficient repair of DNA damaged by ionizing radiation or chemical agents in these mutants revealed proteins essential in this pathway. Early signaling proteins in the checkpoint pathway are members of a family of phosphatidylinositol 3-kinases, rad3 in yeast and ATR in vertebrates, that are believed to localize to sites of DNA damage. [7]
DNA repair processes and cell cycle checkpoints have been intimately linked with cancer due to their functions regulating genome stability and cell progression, respectively. The precise molecular mechanisms that connect dysfunctions in these pathways to the onset of particular cancers are not well understood in most cases. [ 32 ]
After rapid chromatin remodeling, cell cycle checkpoints may be activated to allow DNA repair to be completed before the cell cycle progresses. First, two kinases , ATM and ATR , are activated within 5 or 6 minutes after DNA is damaged.
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.
Before proceeding to mitotic phase, cells must be checked at the G 2 checkpoint for any DNA damage within the chromosomes. The G 2 checkpoint is mainly regulated by the tumor protein p53. If the DNA is damaged, p53 will either repair the DNA or trigger the apoptosis of the cell.
Mediator of DNA damage checkpoint protein 1 is a 2080 amino acid long protein that in humans is encoded by the MDC1 gene [5] [6] [7] located on the short arm (p) of chromosome 6. MDC1 protein is a regulator of the Intra-S phase and the G2/M cell cycle checkpoints and recruits repair proteins to the site of DNA damage.
Nucleotide excision repair is a DNA repair mechanism. [2] DNA damage occurs constantly because of chemicals (e.g. intercalating agents ), radiation and other mutagens . Three excision repair pathways exist to repair single stranded DNA damage: Nucleotide excision repair (NER), base excision repair (BER), and DNA mismatch repair (MMR).