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Postreplication repair is the
repair The technical meaning of maintenance involves functional checks, servicing, repairing or replacing of necessary devices, equipment, machinery, building infrastructure, and supporting utilities in industrial, business, and residential installa ...
of damage to the DNA that takes place after replication. Some example genes in humans include: * BRCA2 and
BRCA1 Breast cancer type 1 susceptibility protein is a protein that in humans is encoded by the ''BRCA1'' () gene. Orthologs are common in other vertebrate species, whereas invertebrate genomes may encode a more distantly related gene. ''BRCA1'' is a ...
*
BLM BLM most commonly refers to: * Black Lives Matter, an international anti-racism movement and organization * Bureau of Land Management, a U.S. federal government agency BLM may also refer to: Organizations * BLM (law firm), United Kingdom and ...
*
NBS1 Nibrin, also known as NBN or NBS1, is a protein which in humans is encoded by the ''NBN'' gene. Function Nibrin is a protein associated with the repair of double strand breaks (DSBs) which pose serious damage to a genome. It is a 754 amino ac ...
Accurate and efficient DNA replication is crucial for the health and survival of all living organisms. Under optimal conditions, the replicative DNA polymerases ε, δ, and α can work in concert to ensure that the genome is replicated efficiently with high accuracy in every cell cycle. However, DNA is constantly challenged by exogenous and endogenous genotoxic threats, including solar ultraviolet (UV) radiation and reactive oxygen species (ROS) generated as a byproduct of cellular metabolism. Damaged DNA can act as a steric block to replicative polymerases, thereby leading to incomplete DNA replication or the formation of secondary DNA strand breaks at the sites of replication stalling. Incomplete DNA synthesis and DNA strand breaks are both potential sources of genomic instability. An arsenal of DNA repair mechanisms exists to repair various forms of damaged DNA and minimize genomic instability. Most DNA repair mechanisms require an intact DNA strand as template to fix the damaged strand. DNA damage prevents the normal enzymatic synthesis of DNA by the
replication fork In molecular biology, DNA replication is the biological process of producing two identical replicas of DNA from one original DNA molecule. DNA replication occurs in all living organisms acting as the most essential part for biological inheritanc ...
. At damaged sites in the genome, both
prokaryotic A prokaryote () is a single-celled organism that lacks a nucleus and other membrane-bound organelles. The word ''prokaryote'' comes from the Greek πρό (, 'before') and κάρυον (, 'nut' or 'kernel').Campbell, N. "Biology:Concepts & Connec ...
and
eukaryotic Eukaryotes () are organisms whose Cell (biology), cells have a cell nucleus, nucleus. All animals, plants, fungi, and many unicellular organisms, are Eukaryotes. They belong to the group of organisms Eukaryota or Eukarya, which is one of the ...
cells utilize a number of postreplication repair (PRR) mechanisms to complete DNA replication. Chemically modified bases can be bypassed by either error-prone or error-free translesion polymerases, or through genetic exchange with the
sister chromatid A sister chromatid refers to the identical copies (chromatids) formed by the DNA replication of a chromosome, with both copies joined together by a common centromere. In other words, a sister chromatid may also be said to be 'one-half' of the dup ...
. The replication of DNA with a broken sugar-phosphate backbone is most likely facilitated by the
homologous recombination Homologous recombination is a type of genetic recombination in which genetic information is exchanged between two similar or identical molecules of double-stranded or single-stranded nucleic acids (usually DNA as in cellular organisms but may ...
proteins that confer resistance to ionizing radiation. The activity of PRR enzymes is regulated by the
SOS response The SOS response is a global response to DNA damage in which the cell cycle is arrested and DNA repair and mutagenesis is induced. The system involves the RecA protein (Rad51 in eukaryotes). The RecA protein, stimulated by single-stranded DNA ...
in bacteria and may be controlled by the
postreplication checkpoint A postreplication checkpoint is a DNA damage checkpoint response that provides time for the repair of daughter-strand gaps generated by the eukaryotic replication fork at sites of DNA damage DNA repair is a collection of processes by which a c ...
response in eukaryotes. The elucidation of PRR mechanisms is an active area of
molecular biology Molecular biology is the branch of biology that seeks to understand the molecular basis of biological activity in and between cells, including biomolecular synthesis, modification, mechanisms, and interactions. The study of chemical and physi ...
research, and the terminology is currently in flux. For instance, PRR has recently been referred to as "DNA damage tolerance" to emphasize the instances in which postreplication DNA damage is repaired without removing the original chemical modification to the DNA. While the term PRR has most frequently been used to describe the repair of single-stranded postreplication gaps opposite damaged bases, a more broad usage has been suggested. In this case, the term PRR would encompasses all processes that facilitate the replication of damaged DNA, including those that repair replication-induced
double-strand breaks DNA repair is a collection of processes by which a cell identifies and corrects damage to the DNA molecules that encode its genome. In human cells, both normal metabolic activities and environmental factors such as radiation can cause DNA dama ...
. Melanoma cells are commonly defective in postreplication repair of DNA damages that are in the form of cyclobutane
pyrimidine dimer Pyrimidine dimers are molecular lesions formed from thymine or cytosine bases in DNA via photochemical reactions, commonly associated with direct DNA damage. Ultraviolet light (UV; particularly UVB) induces the formation of covalent linkages b ...
s, a type of damage caused by
ultraviolet Ultraviolet (UV) is a form of electromagnetic radiation with wavelength from 10 nm (with a corresponding frequency around 30  PHz) to 400 nm (750  THz), shorter than that of visible light, but longer than X-rays. UV radiation ...
radiation. A particular repair process that appears to be defective in melanoma cells is
homologous recombination Homologous recombination is a type of genetic recombination in which genetic information is exchanged between two similar or identical molecules of double-stranded or single-stranded nucleic acids (usually DNA as in cellular organisms but may ...
al repair. Defective postreplication repair of cyclobutane pyrimidine dimers can lead to
mutation In biology, a mutation is an alteration in the nucleic acid sequence of the genome of an organism, virus, or extrachromosomal DNA. Viral genomes contain either DNA or RNA. Mutations result from errors during DNA replication, DNA or viral repl ...
s that are the primary driver of melanoma.


References

{{DNA repair DNA repair