Mismatched nucleotide repair

Mismatched nucleotide repair is a system for detecting and repairing insertions, omissions and mismatches of nucleotides that occur during DNA replication and recombination , as well as some types of DNA damage ^[1] ^[2] .

The fact of erroneous pairing does not allow correcting the error, since it can be on either of the two DNA strands. However, pairing errors, as a rule, are localized on only one (daughter) DNA strand, which avoids the ambiguity in interpreting the error. In gram-positive bacteria, the original DNA strand is methylated, and the daughter strand remains unmethylated for some time. The mechanism of recognition of the initial and daughter threads in other prokaryotes and eukaryotes is currently unclear ^[3] . It is assumed that their daughter DNA strand contains cuts, which are then removed by DNA ligase.

The probability of error in DNA replication is 10 ^–7 –10 ^–8 . The system of repair of mistakenly paired nucleotides reduces this probability to ^10–9 ^[4] .

The repair process consists in recognizing the defect, determining the source and daughter DNA strands, removing the erroneously included nucleotide and replacing it with the correct nucleotide. Usually, not only the wrong nucleotide is removed, but also part of the DNA strand around it, after which the daughter strand is restored using the main strand as a matrix ^[5] .

Content

Repair Proteins

The repair of erroneously paired nucleotides is an extremely conservative process, inherited almost completely from eukaryotes from prokaryotes. This type of repair was first detected in S. pneumoniae (HexA and HexB genes). Further studies of E. coli revealed a number of genes whose blocking causes a sharp increase in the level of mutations. Proteins encoded by these genes are the main active components of the repair system and are indicated by the prefix “Mut”: MutS, MutH and MutL (MutS and MutL are HexA and HexB homologs, respectively).

MutS forms a dimer (MutS ₂ ), which recognizes an abnormal nucleotide on a daughter DNA strand and binds to a defective DNA site. MutH binds to the half methylated DNA region, but does not perform any action until it is activated by the MutL dimer (MutL ₂ ), which serves as a mediator between MutS ₂ and MutH, activating the latter. The DNA helix uncovers in search of the methylated GATC group closest to the defect, which can be located at a distance of 1000 nucleotides or more. MutH cuts the daughter DNA strand near the methylated group and activates one of the UvrABC helicase , which separates the daughter strand from the main one and cuts it off in the region of the defect, including the defect itself and the nucleotides closest to it. The endonuclease used depends on which side (3 'or 5') of the MutH defect cuts the DNA strand. If the cut is made on the 5 'side, RecJ or ExoVII is used, if on the 3' side, then ExoI. The resulting single-stranded region is filled with DNA polymerase III, which uses the main strand as a sample, and then the broken DNA strand is cross - linked with DNA ligase and methylated with methylase ^[5] .

MutS homologues

Binding to DNA, MutS ₂ deforms the helix and covers about 20 nucleotide pairs. It has weak adenosine triphosphatase properties and by binding to ATP forms the tertiary structure of the molecule. X-ray diffraction analysis shows that the structure of the MutS molecule is exceptionally asymmetric, and although the active configuration is a dimer, only one of the monomers interacts with the defective DNA region.

In eukaryotes, two heterodimers were discovered as homologues of MutS: Msh2 / Msh6 (MutSα) and Msh2 / Msh3 (MutSβ). MutSα is used to repair nucleotide substitutions and small loops resulting from insertion or deletion of nucleotide chains. MutSβ removes only long loops (10 or more nucleotides) ^[6] .

MutL homologues

MutL also has weak adenosine triphosphatase properties (uses ATP to move along a DNA strand). It forms a complex with MutS and MutH, expanding the site of interaction of MutS with DNA.

Notes

↑ Iyer R., Pluciennik A., Burdett V., Modrich P. DNA mismatch repair: functions and mechanisms (English) // Chem Rev : journal. - 2006. - Vol. 106 , no. 2 . - P. 302—323 . - DOI : 10.1021 / cr0404794 . - PMID 16464007 .
↑ Larrea AA, Lujan SA, Kunkel TA DNA mismatch repair (English) // Cell . - Cell Press 2010. - Vol. 141 , no. 4 . - P. 730 . - DOI : 10.1016 / j.cell.2010.05.05.002 . - PMID 20478261 .
↑ Modrich Paul. Strand-specific Mismatch Repair in Mammalian Cells // Journal of Biological Chemistry. - 1997 .-- 3 October ( vol. 272 , no. 40 ). - P. 24727-24730 . - ISSN 0021-9258 . - DOI : 10.1074 / jbc.272.40.24727 . - PMID 9312062 .
↑ James A. Shapiro Evolution: A View from the 21st Century . FT Press Science, 2011, 254 p., ISBN 978-0-13-278093-3 .
↑ ¹ ² Cline Susan D. , Hanawalt Philip C. Who's on first in the cellular response to DNA damage? (Eng.) // Nature Reviews Molecular Cell Biology. - 2003 .-- May ( vol. 4 , no. 5 ). - P. 361-373 . - ISSN 1471-0072 . - DOI : 10.1038 / nrm1101 . - PMID 12728270 .
↑ MARRA Giancarlo , SCHÄR Primo. Recognition of DNA alterations by the mismatch repair system (Eng.) // Biochemical Journal. - 1999 .-- February 15 ( vol. 338 , no. 1 ). - P. 1 . - ISSN 0264-6021 . - DOI : 10.1042 / 0264-6021: 3380001 . - PMID 9931291 .

Links

Sung-Hoon Jun, Tae Gyun Kim, Changill Ban DNA mismatch repair system. Classical and fresh roles . FEBS Journal 273 (2006) 1609-1619, doi: 10.1111 / j.1742-4658.2006.05190.x.
DNA Repair
MeSH DNA + Mismatch + Repair
Hsieh P., Yamane K. DNA mismatch repair: Molecular mechanism, cancer, and ageing // Mech Ageing Dev: journal. - 2008 .-- Vol. 129 , no. 7-8 . - P. 391-407 . - DOI : 10.1016 / j.mad.2008.02.012 . - PMID 18406444 .
Iyer R., Pluciennik A., Burdett V., Modrich P. DNA mismatch repair: functions and mechanisms (English) // Chem Rev : journal. - 2006. - Vol. 106 , no. 2 . - P. 302—323 . - DOI : 10.1021 / cr0404794 . - PMID 16464007 .
Joseph N., Duppatla V., Rao DN Prokaryotic DNA mismatch repair (neopr.) // Prog. Nucleic Acid Res. Mol. Biol .. - 2006 .-- T. 81 . - S. 1-49 . - DOI : 10.1016 / S0079-6603 (06) 81001-9 . - PMID 16891168 .
Yang W. Structure and function of mismatch repair proteins (neopr.) // Mutation Research . - Elsevier , 2000. - T. 460 , No. 3-4 . - S. 245-256 . - PMID 10946232 .
Griffith, Wessler, Lewontin, Gelbart, Suzuki, Miller, Introduction to Genetic Analysis , 8th Edition, WH Freeman and Company, ISBN 0-7167-4939-4
Thomas A. Kunkel and Dorothy A. Erie, (2005), DNA Mismatch Repair, Annu Rev. Biochem 74: 681-710
Errol C. Friedberg, Graham C. Walker, Wolfram Siede, Richard D. Wood, Roger A. Schultz, Tom Ellenberger, DNA repair and Mutagenesis, 2nd edition, ASM press, ISBN 1-55581-319-4
Mismatch repair mismatch repair on human biology site.
MutL protein on the site "Human Biology".
Glaser V.M. Gene conversion at the Scientific Network website.
Reparation on the site "Chemical Encyclopedia".
Hsieh, P. Molecular mechanisms of DNA mismatch repair. Mutat. Res. 486, 71–87 (2001).

[1] Iyer R., Pluciennik A., Burdett V., Modrich P. DNA mismatch repair: functions and mechanisms (English) // Chem Rev : journal. - 2006. - Vol. 106 , no. 2 . - P. 302—323 . - DOI : 10.1021 / cr0404794 . - PMID 16464007 .

[2] Larrea AA, Lujan SA, Kunkel TA DNA mismatch repair (English) // Cell . - Cell Press 2010. - Vol. 141 , no. 4 . - P. 730 . - DOI : 10.1016 / j.cell.2010.05.05.002 . - PMID 20478261 .

[modrich-3] Modrich Paul. Strand-specific Mismatch Repair in Mammalian Cells // Journal of Biological Chemistry. - 1997 .-- 3 October ( vol. 272 , no. 40 ). - P. 24727-24730 . - ISSN 0021-9258 . - DOI : 10.1074 / jbc.272.40.24727 . - PMID 9312062 .

[shapiro-4] James A. Shapiro Evolution: A View from the 21st Century . FT Press Science, 2011, 254 p., ISBN 978-0-13-278093-3 .

[susan-5] ¹ ² Cline Susan D. , Hanawalt Philip C. Who's on first in the cellular response to DNA damage? (Eng.) // Nature Reviews Molecular Cell Biology. - 2003 .-- May ( vol. 4 , no. 5 ). - P. 361-373 . - ISSN 1471-0072 . - DOI : 10.1038 / nrm1101 . - PMID 12728270 .

[marra-6] MARRA Giancarlo , SCHÄR Primo. Recognition of DNA alterations by the mismatch repair system (Eng.) // Biochemical Journal. - 1999 .-- February 15 ( vol. 338 , no. 1 ). - P. 1 . - ISSN 0264-6021 . - DOI : 10.1042 / 0264-6021: 3380001 . - PMID 9931291 .