Editing Genetic transformation (section)

===Transformation, as an adaptation for DNA repair===

Competence is specifically induced by DNA damaging conditions.  For instance, transformation is induced in ''Streptococcus pneumoniae'' by the DNA damaging agents mitomycin C (a DNA cross-linking agent) and fluoroquinolone (a topoisomerase inhibitor that causes double-strand breaks).<ref>{{cite journal | vauthors = Claverys JP, Prudhomme M, Martin B | title = Induction of competence regulons as a general response to stress in gram-positive bacteria | journal = Annual Review of Microbiology | volume = 60 | pages = 451–75 | year = 2006 | pmid = 16771651 | doi = 10.1146/annurev.micro.60.080805.142139 }}</ref>  In ''B. subtilis'', transformation is increased by UV light, a DNA damaging agent.<ref>{{cite journal | vauthors = Michod RE, Wojciechowski MF, Hoelzer MA | title = DNA repair and the evolution of transformation in the bacterium Bacillus subtilis | journal = Genetics | volume = 118 | issue = 1 | pages = 31–9 | date = January 1988 | doi = 10.1093/genetics/118.1.31 | pmid = 8608929 | pmc = 1203263 | url = http://www.genetics.org/cgi/pmidlookup?view=long&pmid=8608929 }}</ref> In ''Helicobacter pylori'', ciprofloxacin, which interacts with DNA gyrase and introduces double-strand breaks, induces expression of competence genes, thus enhancing the frequency of transformation<ref>{{cite journal | vauthors = Dorer MS, Fero J, Salama NR | title = DNA damage triggers genetic exchange in Helicobacter pylori | journal = PLOS Pathogens | volume = 6 | issue = 7 | pages = e1001026 | date = July 2010 | pmid = 20686662 | pmc = 2912397 | doi = 10.1371/journal.ppat.1001026 | editor1-last = Blanke | editor1-first = Steven R | doi-access = free }}</ref> Using ''Legionella pneumophila'', Charpentier et al.<ref name=Charpentier>{{cite journal | vauthors = Charpentier X, Kay E, Schneider D, Shuman HA | title = Antibiotics and UV radiation induce competence for natural transformation in Legionella pneumophila | journal = Journal of Bacteriology | volume = 193 | issue = 5 | pages = 1114–21 | date = March 2011 | pmid = 21169481 | pmc = 3067580 | doi = 10.1128/JB.01146-10 }}</ref> tested 64 toxic molecules to determine which of these induce competence. Of these, only six, all DNA damaging agents, caused strong induction. These DNA damaging agents were mitomycin C (which causes DNA inter-strand crosslinks), norfloxacin, ofloxacin and nalidixic acid (inhibitors of DNA gyrase that cause double-strand breaks<ref>{{cite journal | vauthors = Albertini S, Chételat AA, Miller B, Muster W, Pujadas E, Strobel R, Gocke E | title = Genotoxicity of 17 gyrase- and four mammalian topoisomerase II-poisons in prokaryotic and eukaryotic test systems | journal = Mutagenesis | volume = 10 | issue = 4 | pages = 343–51 | date = July 1995 | pmid = 7476271 | doi = 10.1093/mutage/10.4.343 }}</ref>), bicyclomycin (causes single- and double-strand breaks<ref>{{cite journal | vauthors = Washburn RS, Gottesman ME | title = Transcription termination maintains chromosome integrity | journal = Proceedings of the National Academy of Sciences of the United States of America | volume = 108 | issue = 2 | pages = 792–7 | date = January 2011 | pmid = 21183718 | pmc = 3021005 | doi = 10.1073/pnas.1009564108 | bibcode = 2011PNAS..108..792W | doi-access = free }}</ref>), and hydroxyurea (induces DNA base oxidation<ref>{{cite journal | vauthors = Sakano K, Oikawa S, Hasegawa K, Kawanishi S | title = Hydroxyurea induces site-specific DNA damage via formation of hydrogen peroxide and nitric oxide | journal = Japanese Journal of Cancer Research | volume = 92 | issue = 11 | pages = 1166–74 | date = November 2001 | pmid = 11714440 | pmc = 5926660 | doi = 10.1111/j.1349-7006.2001.tb02136.x }}</ref>). UV light also induced competence in ''L. pneumophila''. Charpentier et al.<ref name=Charpentier /> suggested that competence for transformation probably evolved as a DNA damage response.  Natural transformation in the extraordinarily radiation resistant bacterium ''[[Deinococcus radiodurans]]'' is associated with the [[DNA repair|repair of DNA damage]] under stressful conditions.<ref>{{cite journal |vauthors=Sharma DK, Soni I, Rajpurohit YS |title=Surviving the storm: exploring the role of natural transformation in nutrition and DNA repair of stressed Deinococcus radiodurans |journal=Appl Environ Microbiol |volume=91 |issue=1 |pages=e0137124 |date=January 2025 |pmid=39651863 |pmc=11784314 |doi=10.1128/aem.01371-24 |url=}}</ref>
 
Logarithmically growing bacteria differ from stationary phase bacteria with respect to the number of genome copies present in the cell, and this has implications for the capability to carry out an important [[DNA repair]] process. During logarithmic growth, two or more copies of any particular region of the chromosome may be present in a bacterial cell, as cell division is not precisely matched with chromosome replication. The process of homologous recombinational repair (HRR) is a key DNA repair process that is especially effective for repairing double-strand damages, such as double-strand breaks. This process depends on a second homologous chromosome in addition to the damaged chromosome. During logarithmic growth, a DNA damage in one chromosome may be repaired by HRR using sequence information from the other homologous chromosome. Once cells approach stationary phase, however, they typically have just one copy of the chromosome, and HRR requires input of homologous template from outside the cell by transformation.<ref name=Bernstein>{{cite book| vauthors = Bernstein H, Bernstein C, Michod RE | year = 2012 | chapter = Chapter 1: DNA repair as the primary adaptive function of sex in bacteria and eukaryotes | title = DNA Repair: New Research | veditors = Kimura S, Shimizu S | publisher =  Nova Sci. Publ., Hauppauge, N.Y. | pages = 1–49 | isbn = 978-1-62100-808-8 | chapter-url =https://www.novapublishers.com/catalog/product_info.php?products_id=31918 }}</ref>
 
To test whether the adaptive function of transformation is repair of DNA damages, a series of experiments were carried out using ''B. subtilis'' irradiated by UV light as the damaging agent (reviewed by Michod et al.<ref>{{cite journal | vauthors = Michod RE, Bernstein H, Nedelcu AM | title = Adaptive value of sex in microbial pathogens | journal = Infection, Genetics and Evolution | volume = 8 | issue = 3 | pages = 267–85 | date = May 2008 | pmid = 18295550 | doi = 10.1016/j.meegid.2008.01.002 | bibcode = 2008InfGE...8..267M | url = http://www.hummingbirds.arizona.edu/Faculty/Michod/Downloads/IGE%20review%20sex.pdf }}</ref> and Bernstein et al.<ref name=Bernstein />) The results of these experiments indicated that transforming DNA acts to repair potentially lethal DNA damages introduced by UV light in the recipient DNA. The particular process responsible for repair was likely HRR.  Transformation in bacteria can be viewed as a primitive sexual process, since it involves interaction of homologous DNA from two individuals to form recombinant DNA that is passed on to succeeding generations. Bacterial transformation in prokaryotes may have been the ancestral process that gave rise to meiotic sexual reproduction in eukaryotes (see [[Evolution of sexual reproduction]]; [[Meiosis]].)