DNA repair recombinational

It should be noted that HATs and HDACs are not only limited to histones, but rather various nonhistone proteins can be acetylated/deacetylated as well [2, 4]. Many regulators of DNA repair, recombination and replication, viral proteins, classic metabolic enzymes (e.g. bacterial and mammalian acetyl-CoA synthases) and... 

All DNA synthesis required for DNA repair, recombination, and replication depends on the ability of DNA polymerases to recognize the template and correctly insert the complementary nucleotide. The mechanisms whereby these enzymes achieve this tremendous task has been a central topic of interest since the discovery of the first DNA polymerase, E. coli DNA polymerase I, by Arthur Kornberg approximately half a century ago [1], Since then enormous efforts from scientists in many disciplines have been undertaken to gain insights into the complex mechanisms and functions of these molecular machines. 

The protein products of these genes play roles in DNA repair, recombination, and regulation of transcription. A second example, HNPCC (hereditary non-polyposis colorectal cancer), was previously introduced in Chapter 13. It results from inherited mutations in enzymes involved in the DNA mismatch repair system. 

A large number of proteins involved in DNA repair, recombination and replication have been shown to be induced when required (18-20). The SOS response in E. coli, which coordinates the expression of over twenty genes, is probably the best understood model system demonstrating the functional orientation of transcriptionally induced genes (21). This response to... 

The covalent joining of polynucleotides catalyzed by the DNA ligase is a necessary event in DNA repair, recombination, and most notably DNA replication which requires the joining of Okazaki fragments (the small, nascent ssDNA fragments generated from the copying of the minus strand). Initially searched for... 

Mitomycin C was found to have broad activity against a range of tumors and has been used clinically since the early 1960s [14, 15]. It causes many specific cellular effects, including inhibition of DNA synthesis, recombination, chromosome breakage, sister chromatid exchange, induction of DNA repair, and induction of... 

Genetic recombination arises by exchange of homologous segments of DNA between viral genomes, most often during the replication process. The enzymes involved in recombination are DNA polymerases, endonucleases, and ligases, which also play a role in DNA repair and synthesis processes. 

Most DNA manipulations require the use of purified enzymes. Within cells these enzymes are used for DNA replication and transcription, breakdown of foreign DNA, repair of mutated DNA and recombination between different DNA molecules. Most of the purified enzymes are available commercially. They are usually supplied in Tris buffer containing 50% glycerol and are stored at -20 °C. The glycerol is included in the buffer to prevent freezing but must be removed prior to use as it alters the activity of some enzymes. 

Our approach recently developed utilizes DNA repair- or recombination-deficient mutants of the yeast Saccharomyces cerevisiae [8]. An important feature of many tumor cells is that they have defects in their ability to repair damage to DNA as compared with normal cells, suggesting that agents with selective toxicity towards repair-deficient cells might be potential anticancer agents. 

A role for nucleolin in DNA replication, recombination and repair is suggested by its ability to bind directly both DNA and proteins involved in these processes... 

Several enzymatic properties of nucleolin support a role for this protein in DNA repair and recombination it is able to bend DNA (Hanakahi and Maizels, 2000) and can either unwind double-stranded DNA or enhance annealing of complementary DNA strands (Hanakahi and Maizels, 2000 Nasirudin etai, 2005 Sapp et al, 1986 Tuteja et al, 1995). 

Interestingly, nucleolin interacts with several key DNA repair and recombination proteins. First of ah, it interacts with topoisomerase I through its N terminus (Bharti et al, 1996 Edwards et al, 2000). This interaction does not modify the enzymatic activity of topoisomerase I per se, but it could play important role in its predominantly nucleolar localization as it was demonstrated in yeast (Edwards... 

The enzyme catalyzing the addition of ADP-ribose units onto the histones and itself is poly(ADP-ribose) polymerase or synthetase. Poly(ADP-ribose) polymerase is a nuclear, DNA-dependent enzyme that is stimulated by DNA breaks [302]. This property of the enzyme would target its action to sites that have DNA strand breaks (regions of the genome involved in replication, repair, recombination). The enzyme is associated with chromatin areas and perichromatin regions in interphase Chinese hamster ovary cells [312]. Degradation of the ADP-ribose polymer is catalyzed by the nuclear enzyme poly(ADP-ribose) glycohydrolase and ADP-ribosyl protein lyase. 

As described above, histones are much more than passive structural players within chromatin. Dynamic post-translational modifications of these proteins confer specialized chemical proprieties to chromatin of both informational and structural nature with important functional implications. The highly conserved sites for acetylation, methylation, phosphorylation, ADP-ribosylation, and ubiquitination events on histone tails appear to orchestrate functional activities that range from transcriptional activation and repression to DNA repair and recombination. 

Fig. 1. Proteins in DNA repair pathways. DNA repair proteins are listed for each of the following pathways BER (Base Excision Repair), NER (Nucleotide Excision Repair), MMR (Mismatch Repair), HR (Homologous Recombination), and NHEJ (Nonhomologous End Joining). PARP1/2 and BRCA1/2 are relevant in BER and HR pathways, respectively.

DNA repair pathways can be divided into those that respond to SSB and those that respond to DSB. SSB repair pathways include base excision repair (BER), mismatch repair (MMR), and nucleotide excision repair (NER). DSB repair pathways include nonhomologous end joining (NHEJ) and homologous recombination (HR). The proteins involved in these DNA repair pathways are shown in Fig. 1. 

---