- single strand break (SSB)
- double strand break (DSB)
- DSB repair
- general or homologous recombination (HR)
- in Bacteria it occurs according to the Holliday model : it is mediated by the helicase and endonuclease RecBCD => integrase RecA => ligase ==Holliday junction (synapse) ==nick translation==isomerization===1st breakage==1st ligation==2nd breakage==2nd ligation==> if the chromosome separation occurs along one axis recombination results, if it occurs on the perpendicular axis, recombination doesn't occur.
- in Eukarya it occurs according to the Meselson-Radding model : it is mediated by MUS81 endonuclease or homolog of yeast EME1 endonuclease => exonuclease => DNA polymerase
- KU70
- KU80 / XRCC5
-
H2AX
(phosphorylation on serine residues 136 and 139 is crucial for its ability
to prevent genomic instability)
- NBS1
- MRE11A
- MRE11B
- RAD50
- ATP-dependent DNA ligase IV
- XRCC4
-
BLM
(which encodes a RecQ helicase and whose mutations give rise to Bloom's
syndrome
)
forms an evolutionarily conserved complex with human topoisomerase III
(hTOPO III : a,
b,
b2
paralogous isoforms), which can break and rejoin DNA to alter its topology.
The mechanism (double-junction dissolution) is distinct from classical
Holliday junction resolution and prevents exchange of flanking sequences.
Loss of such an activity explains many of the cellular phenotypes of Bloom's
syndrome (e.g. elevated frequency of sister chromatid exchanges (SCE)) - non-homologous end-joining (NHEJ) is the main pathway for resection and repair of DSBs with incompatible ends in mammalian cells. Mycobacterium tuberculosis DNA repair ligase, Mt-Lig, has domains exhibiting significant homology with polymerases and possibly nucleases. Purified recombinant Mt-Lig was an efficient DNA-dependent DNA polymerase in template-dependent primer extension assays and similarly acted as a DNA-dependent RNA polymerase. Mt-Lig possessed 3' to 5' single-strand DNA exonuclease activity, progressively digesting the 3' but not the 5' single strand tails of partial duplexes until reaching the double-strand region. In addition, in polymerization assays with oligonucleotides that produce a nonligatable 1-nt gap upon alignment, Mt-Lig efficiently filled in the gap with no detectable strand displacement synthesis. Mt-Lig used adenosine triphosphate (ATP) and, to a lesser extent, dATP to extend single-strand DNA, demonstrating terminal transferase activity, which is implicated in NHEJ. Mt-Lig could join aligned DNA duplexes possessing a 1-nt 3' flap adjacent to a 3-nt gap. Sequencing of ligated junctions in equivalent assays with substrates with a 3-nt flap adjacent to a 5-nt gap showed the microhomology sequence was retained and bases complementary to the template strand replaced the mismatched flap. Introducing plasmids that express Mt-Ku and Mt-Lig restored NHEJ to about half its level in wildtype yeast. As prokaryotes lack histones, this Mt activity suggests a specific histone interaction is not required during NHEJref.
In a discovery that has flabbergasted geneticists, researchers have shown that plants can overwrite the genetic code they inherit from their parents, and revert to that of their grandparents. The finding challenges textbook rules of inheritance, which state that children simply receive combinations of the genes carried by their parents. The principle was famously established by Austrian monk Gregor Mendel in his nineteenth-century studies on pea plants, but not all genes are so well behaved. Plants, and perhaps other organisms including humans, might possess a back-up mechanism that can bypass unhealthy sequences from their parents and revert to the healthier genetic code possessed by their grandparents or great-grandparents. When studying a particular strain of the cress plant Arabidopsis, which carries a mutation in both copies of a gene called HOTHEAD. In mutated plants, the petals and other flower parts are abnormally fused together. Because these plants pass the mutant gene on to their offspring, conventional genetics dictates that they will also have fused flowers. Not so: Pruitt's team has known for some time that around 10% of the offspring have normal flowers. Using genetic sequencing, the researchers showed that this second generation of plants had rewritten the DNA sequence of one or both of their HOTHEAD genes. They had replaced the abnormal code of their parents with the regular code possessed by earlier generations. And when the team studied numerous other genes, it found that the plants had often edited those back to their ancestral form too. The discovery has left geneticists reeling. It's a mechanism that no one had any idea existed. Researchers are struggling to explain exactly how the plants could rewrite their genetic code. To do that, they need a template that can be passed from one generation to the next. One possibility is that the plants use an extra copy of a gene perched elsewhere in their DNA. But this seems unlikely, because the team found that the plants can rewrite the code of genes that have no similar copies elsewhere in the genome. Instead, the plants carry a previously undiscovered store of the related molecule RNA, that acts as a backup copy of DNA. Such molecules could be passed into pollen or seeds along with DNA and used as a template to correct certain genes. It's the most likely explanation. This type of gene correction goes on in Arabidopsis under normal conditions, just very rarely : it is ramped up when the HOTHEAD gene is mutated, perhaps because the plant becomes stressed. Indeed, the process could exist because it helps plants to survive whenever they find themselves in difficult condition, such as when water or nutrients become scarce. Such stress could trigger plants to revert to the genetic code of their ancestors, which is perhaps more hardy than that of their parents. To test this, Pruitt is examining whether stressful situations do indeed prompt the same phenomenon. A similar process might even go on in humans. This is suggested by rare cases of children who inherit disease-causing mutations but show only mild symptoms, perhaps because some of their cells have reverted to a normal and healthier genetic code. If humans do correct their genes in this way, the procedure might be usefully hijacked by researchers or doctors. They might be able to identify the RNA molecules that carry out the repair and use them to correct harmful mutations in patients.
-
conjugation (in Bacteria
and in Protozoa)
: the mechanism responsible for the widespread distribution of antibiotic
resistance genes, gene clusters encoding biodegradative pathways and pathogenicity
determinants
-
transformation (in Bacteria)
-
transduction (in Bacteria
and Eukarya)
: standard mitochondrial genes (rps2, rps11, and atp1)
are subject to frequent HGT between distantly related angiosperms
- general or homologous recombination : for plasmids, transfected DNA, ...
- transpositional recombination : for mobile elements. The integrase translocase or transposase creates a staggered cut in the target site causing a direct duplication at the ends of the inserted transposon that remains even after transposon excision. No homology is needed.
- site-specific recombination : for bacteriophages, gene rearrangements, ...
- illegitimate recombination
