Nonhomologous End-Joining: Mechanisms, Conservation and Relationship to Illegitimate Recombination

Wilson, Thomas E.

doi:10.1007/4735_2006_0210

Cited by 5 publications

(9 citation statements)

References 123 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…By comparative genomic analysis, it appears that loss of introns in teleost genes occurs by incremental steps, one or two introns at a time, through a process of homologous recombination between the cDNA and the genomic sequence encoding that cDNA [30,31]. In contrast, the intronless fabp11a gene most likely arose by illegitimate recombination [32] between the fabp11a cDNA and an unrelated region of the medaka genome.…”

Section: Resultsmentioning

confidence: 99%

“…Duplicate intron‐containing fabp11 genes emerged in the teleost fishes following the WGD [16–19]. A new intronless fabp11a gene arose by integration of a fabp11a cDNA into another gene by illegitimate recombination [32], co‐opting that gene’s promoter and its regulatory elements. Finally, the intron‐containing fabp11a gene was lost from the genome owing to accumulation of deleterious mutations, as the intronless fabp11a gene maintained the function(s) of the intron‐containing gene during its functional decay.…”

Section: Resultsmentioning

confidence: 99%

See 1 more Smart Citation

The evolutionary relationship of the transcriptionally active fabp11a (intronless) and fabp11b genes of medaka with fabp11 genes of other teleost fishes

2012

View full text Add to dashboard Cite

Here we describe the structure of the fatty acid-binding protein 11a and 11b genes (fabp11a and fabp11b) in medaka, and their evolutionary relationship to fabp11 genes from other teleost fishes. Initial studies indicated that the medaka fabp11a gene is intronless, but the fabp11b gene consists of four exons separated by three introns, a genomic organization that is characteristic of most members of the intracellular lipid-binding protein family. Based on genomic sequence, we conclude that the intronless fabp11a gene most likely arose as a result of reverse transcription of its mRNA transcript into cDNA followed by integration into chromosomal DNA. The ancestral intron-containing fabp11a gene was presumably lost from the medaka genome. The duplicated fabp11 genes extant in medaka encode polypeptides of 134 amino acids, which share highest sequence identity and similarity, and cluster in a distinct phylogenetic clade, with their orthologs in other teleost fishes. The fabp11a and fabp11b genes in medaka are therefore orthologs of the fabp11a and fabp11b genes, respectively, of other teleost fishes. No conserved gene synteny was found between medaka fabp11a and fabp11a genes from other teleost fishes, supporting our suggestion as to how this intronless gene arose. However, conserved gene synteny was evident between medaka fabp11b and fabp11b genes from other teleost fishes. The tissue-specific distribution of transcripts for medaka and zebrafish fabp11a and fabp11b genes revealed acquisition of a new function(s) in various tissues by the medaka fabp11b gene, which may explain the retention of sister duplicates of fabp11 in the medaka genome.

show abstract

Section: Resultsmentioning

confidence: 99%

Section: Resultsmentioning

confidence: 99%

The evolutionary relationship of the transcriptionally active fabp11a (intronless) and fabp11b genes of medaka with fabp11 genes of other teleost fishes

2012

View full text Add to dashboard Cite

show abstract

“…cipal mechanism for repairing DNA double-strand breaks (DSBs) in which the two DSB ends are directly rejoined (Wilson 2007). As such, NHEJ is critical for maintaining genome stability.…”

Section: N Onhomologous End Joining (Nhej) Is a Prin-mentioning

confidence: 99%

Recruitment and Dissociation of Nonhomologous End Joining Proteins at a DNA Double-Strand Break in Saccharomyces cerevisiae

2008

View full text Add to dashboard Cite

Nonhomologous end joining (NHEJ) is an important DNA double-strand-break (DSB) repair pathway that requires three protein complexes in Saccharomyces cerevisiae: the Ku heterodimer (Yku70-Yku80), MRX (Mre11-Rad50-Xrs2), and DNA ligase IV (Dnl4-Lif1), as well as the ligase-associated protein Nej1. Here we use chromatin immunoprecipitation from yeast to dissect the recruitment and release of these protein complexes at HO-endonuclease-induced DSBs undergoing productive NHEJ. Results revealed that Ku and MRX assembled at a DSB independently and rapidly after DSB formation. Ligase IV appeared at the DSB later than Ku and MRX and in a strongly Ku-dependent manner. Ligase binding was extensive but slightly delayed in rad50 yeast. Ligase IV binding occurred independently of Nej1, but instead promoted loading of Nej1. Interestingly, dissociation of Ku and ligase from unrepaired DSBs depended on the presence of an intact MRX complex and ATP binding by Rad50, suggesting a possible role of MRX in terminating a NHEJ repair phase. This activity correlated with extended DSB resection, but limited degradation of DSB ends occurred even in MRX mutants with persistently bound Ku. These findings reveal the in vivo assembly of the NHEJ repair complex and shed light on the mechanisms controlling DSB repair pathway utilization.

show abstract

“…As opposed to one‐ended breaks, repair of two‐ended breaks can be accomplished by simply ligating them together. This is achieved by the non‐homologous DNA end‐joining pathway (Figure 1B; Lees‐Miller and Meek, 2003; Lieber et al , 2003; Wilson, 2007).…”

Section: Dna End Metabolism By End Joiningmentioning

confidence: 99%

“…The simplest breaks to be handled by non‐homologous DNA end joining are those with a chemical composition that allows direct ligation. In these cases, joining requires the ‘core’ components of non‐homologous DNA end joining, which include the Ku70/80 heterodimer, the DNA‐dependent protein kinase catalytic subunit (DNA–PKcs), XRCC4, XLF, and DNA ligase IV (Wilson, 2007). The Ku70/80 protein complex plays a central role.…”

Section: Dna End Metabolism By End Joiningmentioning

confidence: 99%

Quality control of DNA break metabolism: in the ‘end’, it's a good thing

Kanaar

Wyman

Rothstein

2008

EMBO J

View full text Add to dashboard Cite

DNA ends pose specific problems in the control of genetic information quality. Ends of broken DNA need to be rejoined to avoid genome rearrangements, whereas natural DNA ends of linear chromosomes, telomeres, need to be stable and hidden from the DNA damage response. Efficient DNA end metabolism, either at induced DNA breaks or telomeres, does not result from the machinelike precision of molecular reactions, but rather from messier, more stochastic processes. The necessary molecular interactions are dynamically unstable, with constructive and destructive processes occurring in competition. In the end, quality control comes from the constant building up and tearing down of inappropriate, but also appropriate reaction steps in combination with factors that only slightly shift the equilibrium to eventually favour appropriate events. Thus, paradoxically, enzymes antagonizing DNA end metabolism help to ensure that genome maintenance becomes a robust process.

show abstract

Nonhomologous End-Joining: Mechanisms, Conservation and Relationship to Illegitimate Recombination

Cited by 5 publications

References 123 publications

The evolutionary relationship of the transcriptionally active fabp11a (intronless) and fabp11b genes of medaka with fabp11 genes of other teleost fishes

The evolutionary relationship of the transcriptionally active fabp11a (intronless) and fabp11b genes of medaka with fabp11 genes of other teleost fishes

Recruitment and Dissociation of Nonhomologous End Joining Proteins at a DNA Double-Strand Break in Saccharomyces cerevisiae

Quality control of DNA break metabolism: in the ‘end’, it's a good thing

Contact Info

Product

Resources

About