What is the DNA damage response pathway?
The DNA damage response (DDR) comprises a set of signaling pathways for the detection and repair of DNA damage and includes the MMR system for mispaired bases, the base excision repair system for small base modifications, the nucleotide excision repair for intrastrand crosslinks and pyrimidine dimers, the single-strand …
What are the 5 DNA repair pathways?
At least five major DNA repair pathways—base excision repair (BER), nucleotide excision repair (NER), mismatch repair (MMR), homologous recombination (HR) and non-homologous end joining (NHEJ)—are active throughout different stages of the cell cycle, allowing the cells to repair the DNA damage.
Which is the major pathway by which DNA base damage is repaired?
The base excision repair (BER) pathway efficiently corrects most non-bulky DNA base lesions that are not addressable by direct reversal. Thus, BER is responsible for repairing the vast majority of lesions that occur in DNA, and the pathway is active in both nuclei and mitochondria.
What are the three major types of damage that occur to DNA?
DNA bases can be damaged by: (1) oxidative processes, (2) alkylation of bases, (3) base loss caused by the hydrolysis of bases, (4) bulky adduct formation, (5) DNA crosslinking, and (6) DNA strand breaks, including single and double stranded breaks. An overview of these types of damage are described below.
What is A DDR mutation?
DDR mutation is associated with enriched immune cell infiltration, enhancement of the cancer immunity cycle, elevated TMB, and abundant immune checkpoint expression in the tumor microenvironment.
What is DDR in oncology?
The DNA Damage Response (DDR) is one of the scientific platforms we are focusing on to improve the clinical paradigm in oncology. Our understanding of the role the DDR plays in cancer is enabling us to push our research further to target a broad range of cancers including difficult to treat or aggressive cancers.
What are 4 DNA damaging agents?
DNA damaging agents are widely used in oncology to treat both hematological and solid cancers. Some commonly used modalities include ionizing radiation, platinum drugs (cisplatin, oxaliplatin, and carboplatin), cyclophosphamide, chlorambucil, and temozolomide.
What is BER pathway?
Base excision repair (BER) corrects small base lesions that do not significantly distort the DNA helix structure. It is initiated by a DNA glycosylase that recognizes and removes the damaged base, leaving an abasic site which is further processed by short-patch repair or long-patch repair.
How many DDR genes are there?
There are at least 450 genes associated with DDR [1, 2]. Some identified examples of DDR genes known to be involved in cancer are shown in the table below.
What is DDR DNA?
The DNA damage response (DDR) involves a complex network of genes responsible for sensing and responding to specific types of DNA damage, encompassing specific machineries mediating DNA repair, cell cycle regulation, replication stress responses and apoptosis.
What is DDR mutation?
What is the most common type of DNA damage?
Single-strand breaks (SSBs) result from disruption of the phosphodiester bond between two adjacent deoxyribose residues in the backbone of DNA. SSBs are among the most common instances of DNA damage. Double-strand breaks (DSBs) are less common in living cells, and their presence is generally not tolerated.
Which DNA repair process responds to single strand breaks?
Activated p53 regulates the process of DNA damage repair, the repair mechanism for single-stranded breaks is NER or BER, and they require the participation of various regulatory factors such as RPA, PCNA, p48 XP, poly ADP-ribose polymerase (PARP), X-ray repair cross-complementary protein1 (XRCC1) and DNA ligase.
Which of the following DNA repair pathways is most likely to lead to chromosomal rearrangements?
DNA double-strand break (DSB) repair occurring in repeated DNA sequences often leads to the generation of chromosomal rearrangements.
How does BER repair DNA?
The BER pathway repairs non-distorting DNA lesions following oxidation, deamination or alkylation of bases in the DNA backbone18. Initially, a damaged base is recognized and removed by a DNA glycosylase that cleaves the N-glycosidic bond between the base and the DNA backbone, generating an AP site (Fig. 1a).
What does DNA glycosylase do?
DNA glycosylases play a key role in the elimination of such DNA lesions; they recognize and excise damaged bases, thereby initiating a repair process that restores the regular DNA structure with high accuracy.
What are the 3 main types of gene mutation linked to genetic diseases?
There are three types of genetic disorders:
- Single-gene disorders, where a mutation affects one gene. Sickle cell anemia is an example.
- Chromosomal disorders, where chromosomes (or parts of chromosomes) are missing or changed.
- Complex disorders, where there are mutations in two or more genes.