DNA-damage repair; the good, the bad, and the ugly. EMBO J

ArticleinThe EMBO Journal 27(4):589-605 · March 2008with547 Reads
Impact Factor: 10.43 · DOI: 10.1038/emboj.2008.15 · Source: PubMed
Abstract
Organisms have developed several DNA-repair pathways as well as DNA-damage checkpoints to cope with the frequent challenge of endogenous and exogenous DNA insults. In the absence or impairment of such repair or checkpoint mechanisms, the genomic integrity of the organism is often compromised. This review will focus on the functional consequences of impaired DNA-repair pathways. Although each pathway is addressed individually, it is essential to note that cross talk exists between repair pathways, and that there are instances in which a DNA-repair protein is involved in more than one pathway. It is also important to integrate DNA-repair process with DNA-damage checkpoints and cell survival, to gain a better understanding of the consequences of compromised DNA repair at both cellular and organismic levels. Functional consequences associated with impaired DNA repair include embryonic lethality, shortened life span, rapid ageing, impaired growth, and a variety of syndromes, including a pronounced manifestation of cancer.

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    • "In addition to its function in DNA replication, Pol δ plays a role in DNA repair and recombination [6]. In base excision repair (BER), one of DNA repair mechanisms of single-stranded DNA damage, Pol δ is involved in the long-path pathway, whereas Pol β plays a role in the short-path pathway [10]. Interestingly, the long-patch BER is predominate in P. falciparum while short-path BER is mainly found in humans [11]. "
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    Preview · Article · Dec 2016 · Malaria Journal
    • "Each repair system is responsible for a specific subset of lesions, although partial overlap can occur depending on the type of DNA lesion that needs to be repaired. At least six DNA repair pathways can be listed in mammalian cells: (1) the direct reversal pathway, which executes the direct reversal of chemical modifications of nucleotides; (2) mismatch repair (MMR), which repairs base pair mismatches; (3) base excision repair (BER), repairing mainly oxidized and alkylation lesions in the nucleus and mitochondria, as well as single-strand breaks; (4) nucleotide excision repair (NER), to correct transcription-disturbing bulky adducts; (5) homologous recombination (HR); and (6) non-homologous end joining (NHEJ), which correct single-and double-strand breaks [10,13]. Telomere maintenance requires further specialized proteins [14]. "
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    • "Efficient DNA repair machinery that removes arising DNA damage, comprising several distinct pathways, ensures effectively genomic integrity. Alterations in the DNA repair increase the vulnerability of the cells, resulting in an accumulation of mutations in the genome, which may ultimately result in tumorigenesis [17]. DNA repair is closely associated with fundamental cellular processes: a) DNA replication -its deregulation occurs through replication-blocking DNA lesions, the activation of certain oncogenes, loss of function of certain tumour suppressors, and promoting replication stress that triggers double-strand breaks (DSB) formation and leads consecutively to unscheduled recombination events and chromosomal rearrangements; b) chromosomal segregation -defects in chromatid cohesion, spindle formation or mitotic checkpoints may lead to aberrant chromosomal segregation; c) telomere maintenance -recognition and signalling of DNA damage is a prerequisite for the induction of subsequent cellular responses such as increased repair, cell cycle arrest and apoptosis [18][19][20]. "
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