What are DNA cross linking agents?
(… KROS-lin-king AY-jent) A substance that binds DNA nucleotides together and blocks DNA synthesis. In cancer treatment, DNA cross-linking agents may kill cancer cells by damaging their DNA and stopping them from dividing.
Is cisplatin a cross linking agent?
Abstract. cis-Diamminedichloroplatinum(II) (cisplatin) is a widely used anticancer drug that binds to and crosslinks DNA. The major DNA adduct of the drug results from coordination of two adjacent guanine bases to platinum to form the intrastrand crosslink cis-[Pt(NH3)2[d(GpG)-N7(1), -N7(2)]] (cis-Pt-GG).
What is Intrastrand?
Adjective. intrastrand (not comparable) Within a strand, especially within a single strand of DNA.
How do the single base alterations in DNA damage occur?
Figure 12.1 Chromosomal Alterations. One type, a point mutation, affects a single base and most commonly occurs when one base is substituted or replaced by another. Mutations also result from the addition of one or more bases, known as an insertion, or the removal of one or more bases, known as a deletion.
How does DNA crosslinking work?
In genetics, crosslinking of DNA occurs when various exogenous or endogenous agents react with two nucleotides of DNA, forming a covalent linkage between them. This crosslink can occur within the same strand (intrastrand) or between opposite strands of double-stranded DNA (interstrand).
What are cross linking DNA damage?
DNA crosslinking damage occurs when crosslinking agents covalently connect two nucleotide residues from the same DNA strand (intrastrand crosslink) or from opposite strands [interstrand crosslink (ICL)]. Intrastrand crosslinks can be readily removed by the nucleotide excision repair (NER) mechanism (1).
What happens in DNA cross linking?
How does formaldehyde cross link DNA?
Formaldehyde crosslinking of biomolecules occurs in two steps. First, formaldehyde reacts with a relatively strong nucleophile, most commonly a lysine ε-amino group from a protein. This reaction forms a methylol intermediate that can lose water to yield a Schiff base (an imine).
How do you cross link DNA?
What factors naturally cause DNA crosslinks?
Naturally occurring crosslinking agents include psoralens, mitomycin C, nitrous acids, etc. Mitomycin C was originally found in fungi with antibiotic activity mediated by its DNA crosslinking ability since bacteria are easily killed by a single unrepaired ICL (5). Psoralens are natural compounds derived from plants.
What are the agents that can damage DNA?
DNA can be damaged via environmental factors as well. Environmental agents such as UV light, ionizing radiation, and genotoxic chemicals. Replication forks can be stalled due to damaged DNA and double strand breaks are also a form of DNA damage.
What are the two main classes of agents that can damage DNA?
DNA damage can be subdivided into two types: (1) endogenous damage caused by reactive oxygen species (ROS) that are derived from metabolic byproducts and (2) exogenous damage caused by radiation (UV, X-ray, gamma), hydrolysis, plant toxins, and viruses.