Академический Документы
Профессиональный Документы
Культура Документы
DNA mismatch repair is a mechanism where the template strand is distinguished from the
lagging strand and the repair proteins are therefore able to review the action of the DNA
polymerase after replication. Defects lead to Hereditary Nonpolyposis Colorectal Cancer.
Nucleotide excision repair is a mechanism which removes a faulty nucleotide and few
adjacent nucleotides before DNA polymerase and DNA ligase repair the broken strand. If it's
defected it leads to the rare disorder Xerdoerma Pigmentosum (XP). A person with XP will
have high mutation rate from UV light and can develop multiple basal cell carcinomas and
other skin malignancies.
A faulty protein arising from a mutant caretaker gene can lead to certain genomic
instabilities such as microsatellites, point mutations, or chromosomal instabilities (7). In
humans, chromosomal instabilities, brought about by chromosomal rearrangement errors, are the
cause of many hereditary predispositions to cancer. Mutations in caretakers could indirectly
initiate tumour formation because the affected cells easily accumulate mutations due to impaired
genome maintenance. However, two knockouts in a caretaker gene, as well as other mutations
within the cell, are required for tumour formation (5).
The PMS2 gene provides instructions for making a protein that plays an essential role in
repairing DNA. This protein helps fix mistakes that are made when DNA is copied (DNA
replication) in preparation for cell division. The PMS2 protein joins with another protein called
MLH1 (produced from the MLH1 gene) to form a protein complex. This complex coordinates the
activities of other proteins that repair mistakes made during DNA replication. Repairs are made
by removing the section of DNA that contains mistakes and replacing it with a corrected DNA
sequence. The PMS2gene is a member of a set of genes known as the mismatch repair (MMR)
genes.
The MSH2 gene provides instructions for making a protein that plays an essential role in DNA
repair. This protein helps fix mistakes that are made when DNA is copied (DNA replication) in
preparation for cell division. The MSH2 protein joins with one of two other proteins, MSH6 or
MSH3 (each produced from a different gene), to form a protein complex. This complex identifies
locations on the DNA where mistakes have been made during DNA replication. Another group of
proteins, the MLH1-PMS2 protein complex, then repairs the errors. The MSH2 gene is a member
of a set of genes known as the mismatch repair (MMR) genes.
Oncogenic causing development of a tumor or tumors
chromosome translocation is a chromosome abnormality ca used by rearrangement of parts
between non-homologous chromosomes
"Caretakers" are genes involved in maintaining genetic stability and minimizing the rate at which
mutations occur in gatekeepers.
Caretaker genes encode products that stabilize the genome. Fundamentally, mutations in
caretaker genes lead to genomic instability. Tumor cells arise from two distinct classes of
genomic instability: mutational instability arising from changes in the nucleotide sequence of
DNA and chromosomal instability arising from improper rearrangement of chromosomes.
Factors that contribute to genome stabilization include proper cell-cycle checkpoints, DNA repair
pathways, and other actions that ensure cell survival following DNA damage.[1] Specific DNA
maintenance operations encoded by caretaker genes include nucleotide excision repair, base