What enzymes are involved in nucleotide excision repair?

The process of nucleotide excision repair is controlled in Escherichia coli by the UvrABC endonuclease enzyme complex, which consists of four Uvr proteins: UvrA, UvrB, UvrC, and DNA helicase II (sometimes also known as UvrD in this complex).

What is ICL repair?

Interstrand DNA crosslinks (ICLs) are the link between Watson-Crick strands of DNAs with the covalent bond and prevent separation of DNA strands. Since the ICL lesion affects both strands of the DNA, the ICL repair is not simple.

How does homologous recombination repair?

In cells that divide through mitosis, homologous recombination repairs double-strand breaks in DNA caused by ionizing radiation or DNA-damaging chemicals. It does so by facilitating chromosomal crossover, in which regions of similar but not identical DNA are exchanged between homologous chromosomes.

Why are interstrand cross links particularly cytotoxic?

Interstrand cross-links (ICLs) are among the most cytotoxic DNA lesions to cells because they prevent the two DNA strands from separating, thereby precluding replication and transcription.

What is DNA nucleotide excision repair?

Nucleotide excision repair (NER) is the main pathway used by mammals to remove bulky DNA lesions such as those formed by UV light, environmental mutagens, and some cancer chemotherapeutic adducts from DNA. Deficiencies in NER are associated with the extremely skin cancer-prone inherited disorder xeroderma pigmentosum.

How does crosslink repair work?

Crosslinked DNA is repaired in cells by a combination of enzymes and other factors from the nucleotide excision repair (NER) pathway, homologous recombination, and the base excision repair (BER) pathway. DNA crosslinks generally cause loss of overlapping sequence information from the two strands of DNA.

What is homologous recombination DNA repair?

Homologous recombination (HR) is a DNA metabolic process found in all forms of life that provides high-fidelity, template-dependent repair or tolerance of complex DNA damages including DNA gaps, DNA double-stranded breaks (DSBs), and DNA interstrand crosslinks (ICLs).

What is homologous DNA repair?

Homologous recombination repair is a DNA repair process that includes the invasion of an undamaged DNA molecule by a damaged molecule of identical or very similar sequence. Resynthesis of the damaged region is accomplished using the undamaged molecule as a template.

What causes interstrand crosslink?

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).

How DNA is repaired by the nucleotide excision repair system?

In nucleotide excision repair (NER), damaged bases are cut out within a string of nucleotides, and replaced with DNA as directed by the undamaged template strand. This repair system is used to remove pyrimidine dimers formed by UV radiation as well as nucleotides modified by bulky chemical adducts.

What is the function of interstrand DNA crosslinks?

Interstrand DNA crosslinks (ICLs) are the link between Watson-Crick strands of DNAs with the covalent bond and prevent separation of DNA strands. Since the ICL lesion affects both strands of the DNA, the ICL repair is not simple.

What are the mechanisms of DNA crosslink repair?

Since the ICL lesion affects both strands of the DNA, the ICL repair is not simple. So far, nucleotide excision repair (NER), structure-specific endonucleases, translesion DNA synthesis (TLS), homologous recombination (HR), and factors responsible for Fanconi anemia (FA) are identified to be involved in ICL repair.

Which is a model of ICL repair in quiescent cells?

Models of ICL repair. a Model of ICL repair in quiescent cells (G0/G1 phase). An ICL on DNA is recognized by NER machinery. In the case of ICL-blocked transcription, two specific factors for transcription-coupled NER, CSA and CSB, are required to load the incision complex.

How does an ICL affect the replication of DNA?

ICLs are extremely cytotoxic, as even a single ICL in the genome can cause severe defects in a variety of vital DNA metabolic processes, such as transcription and DNA replication [ 6, 7 ].