Saccharomyces cerevisiae Meyen ex E.C. Hansen (budding yeast) [SCE]

FULL NAME: DNA mismatch repair protein MSH2


DESCRIPTION:
Component of the post-replicative DNA mismatch repair system (MMR). Forms two different heterodimers: MutS alpha (MSH2-MSH6 heterodimer) and MutS beta (MSH2-MSH3 heterodimer), which bind to DNA mismatches thereby initiating DNA repair. MSH2 seems to act as a scaffold for the other MutS homologs that provide substrate-binding and substrate-specificity. When bound, heterodimers bend the DNA helix and shield approximately 20 base pairs. MutS alpha acts mainly to repair base-base and single insertion-deletion mismatches that occur during replication, but can also repair longer insertion-deletion loops (IDLs), although with decreasing efficiency as the size of the extrahelical loop increases. MutS beta acts mainly to repair IDLs from 2 to 13 nucleotides in size, but can also repair base-base and single insertion-deletion mismatches. After mismatch binding, MutS alpha or beta form a ternary complex with a MutL heterodimer, which is thought to be responsible for directing the downstream MMR events, including strand discrimination, excision, and resynthesis. ATP binding and hydrolysis play a pivotal role in mismatch repair functions. Both subunits bind ATP, but with differing affinities, and their ATPase kinetics are also very different. MSH6 binds and hydrolyzes ATP rapidly, whereas MSH2 catalyzes ATP at a substantially slower rate. Binding to a mismatched base pair suppresses MSH6-catalyzed ATP hydrolysis, but not the activity of MSH2. ATP binding to both subunits is necessary to trigger a change in MutS alpha interaction with mismatched DNA, converting MutS alpha into a sliding clamp capable of hydrolysis-independent movement along DNA, and also facilitates formation of ternary complexes containing MutS and MutL proteins and the mismatch. MutS beta also has a role in regulation of heteroduplex formation during mitotic and meiotic recombination. MutS beta binds to DNA flap structures predicted to form during recombination, and is required for 3' non-homologous tail removal (NHTR). MutS beta-binding alters the DNA conformation of its substrate at the ds/ssDNA junction and may facilitate its recognition and/or cleavage by the downstream nucleotide excision repair (NER) RAD1-RAD10 endonuclease.

MISCELLANEOUS:
Present with 1230 molecules/cell in log phase SD medium.


STRUCTURE SIMILARITY:
Belongs to the DNA mismatch repair mutS family.


ENZYME REGULATION:
Inhibited by Cd(2+).


RELATED PATHWAY(S):
mismatch repair (MMR)


Amino acids sequence

        10         20         30         40         50         60
MSSTRPELKF SDVSEERNFY KKYTGLPKKP LKTIRLVDKG DYYTVIGSDA IFVADSVYHT
        70         80         90        100        110        120
QSVLKNCQLD PVTAKNFHEP TKYVTVSLQV LATLLKLCLL DLGYKVEIYD KGWKLIKSAS
       130        140        150        160        170        180
PGNIEQVNEL MNMNIDSSII IASLKVQWNS QDGNCIIGVA FIDTTAYKVG MLDIVDNEVY
       190        200        210        220        230        240
SNLESFLIQL GVKECLVQDL TSNSNSNAEM QKVINVIDRC GCVVTLLKNS EFSEKDVELD
       250        260        270        280        290        300
LTKLLGDDLA LSLPQKYSKL SMGACNALIG YLQLLSEQDQ VGKYELVEHK LKEFMKLDAS
       310        320        330        340        350        360
AIKALNLFPQ GPQNPFGSNN LAVSGFTSAG NSGKVTSLFQ LLNHCKTNAG VRLLNEWLKQ
       370        380        390        400        410        420
PLTNIDEINK RHDLVDYLID QIELRQMLTS EYLPMIPDIR RLTKKLNKRG NLEDVLKIYQ
       430        440        450        460        470        480
FSKRIPEIVQ VFTSFLEDDS PTEPVNELVR SVWLAPLSHH VEPLSKFEEM VETTVDLDAY
       490        500        510        520        530        540
EENNEFMIKV EFNEELGKIR SKLDTLRDEI HSIHLDSAED LGFDPDKKLK LENHHLHGWC
       550        560        570        580        590        600
MRLTRNDAKE LRKHKKYIEL STVKAGIFFS TKQLKSIANE TNILQKEYDK QQSALVREII
       610        620        630        640        650        660
NITLTYTPVF EKLSLVLAHL DVIASFAHTS SYAPIPYIRP KLHPMDSERR THLISSRHPV
       670        680        690        700        710        720
LEMQDDISFI SNDVTLESGK GDFLIITGPN MGGKSTYIRQ VGVISLMAQI GCFVPCEEAE
       730        740        750        760        770        780
IAIVDAILCR VGAGDSQLKG VSTFMVEILE TASILKNASK NSLIIVDELG RGTSTYDGFG
       790        800        810        820        830        840
LAWAIAEHIA SKIGCFALFA THFHELTELS EKLPNVKNMH VVAHIEKNLK EQKHDDEDIT
       850        860        870        880        890        900
LLYKVEPGIS DQSFGIHVAE VVQFPEKIVK MAKRKANELD DLKTNNEDLK KAKLSLQEVN
       910        920        930        940        950        960
EGNIRLKALL KEWIRKVKEE GLHDPSKITE EASQHKIQEL LRAIANEPEK ENDNYLKYIK

ALLL     

Encoded by MSH2 gene


OTHER NAME(S):
PMS5


Nucleic acid sequence

        10         20         30         40         50         60
atgtcctcca ctaggccaga gctaaaattc tctgatgtat cagaggagag aaacttctat
        70         80         90        100        110        120
aagaagtata cagggttgcc gaagaaacca ttaaaaacca ttagattagt ggataaaggc
       130        140        150        160        170        180
gactattaca cagttatagg ttcagatgcg atatttgtgg cagattcagt ctatcatact
       190        200        210        220        230        240
caatctgttt taaagaactg ccaattggac cctgtaacgg caaagaactt ccatgaacca
       250        260        270        280        290        300
actaaatatg ttactgtttc gctacaagtt cttgccactc tgctgaagtt atgtttgttg
       310        320        330        340        350        360
gatctgggat ataaagttga gatatacgat aagggttgga aattaataaa aagcgcatct
       370        380        390        400        410        420
ccagggaaca ttgagcaagt taatgagcta atgaatatga atattgattc gagtatcatc
       430        440        450        460        470        480
attgcaagtt tgaaagttca atggaattcc caagatggaa actgcattat tggagttgct
       490        500        510        520        530        540
ttcattgata ccactgcata caaggtggga atgcttgata ttgtcgataa tgaagtgtat
       550        560        570        580        590        600
tccaacctag agagtttctt gattcaattg ggtgtaaagg aatgtttggt gcaggacttg
       610        620        630        640        650        660
acatcaaatt caaactccaa tgctgaaatg cagaaagtaa taaatgtaat tgatcgctgt
       670        680        690        700        710        720
gggtgcgtcg ttacattatt gaaaaactca gaattttctg aaaaagatgt cgaactggat
       730        740        750        760        770        780
ttaaccaagt tactgggcga tgatttggca ttatcgttac cacaaaaata ctctaaatta
       790        800        810        820        830        840
tctatgggtg catgcaatgc attgattgga tatttacaat tgctctcaga gcaagatcaa
       850        860        870        880        890        900
gtaggcaagt atgaattagt tgaacataaa ttaaaggagt ttatgaagtt ggatgcctcc
       910        920        930        940        950        960
gctattaaag cccttaattt attcccacaa ggaccacaaa atccatttgg tagcaacaat
       970        980        990       1000       1010       1020
ttagctgtat ctggatttac gagtgctggt aattctggta aagtaacttc tcttttccag
      1030       1040       1050       1060       1070       1080
ttactgaatc attgcaaaac aaatgctggt gttcggcttt taaatgaatg gttgaagcaa
      1090       1100       1110       1120       1130       1140
ccactgacca atattgacga aattaataaa agacatgatt tagtcgacta tctaattgac
      1150       1160       1170       1180       1190       1200
caaatcgagt taagacagat gttgacttct gaatatttac ccatgattcc agatattcgt
      1210       1220       1230       1240       1250       1260
agattgacta agaaattaaa taaaagagga aacttagagg atgtcttgaa aatttaccaa
      1270       1280       1290       1300       1310       1320
ttcagtaaaa gaataccaga aattgttcaa gttttcactt cgttcttgga ggacgacagc
      1330       1340       1350       1360       1370       1380
cccactgaac cagtaaacga actggtccgc tccgtttggc tagctccttt aagccaccac
      1390       1400       1410       1420       1430       1440
gttgaacctt tgtccaaatt cgaagaaatg gttgaaacaa cggttgattt ggatgcttat
      1450       1460       1470       1480       1490       1500
gaagaaaata acgaatttat gattaaagtt gagtttaatg aggaattagg aaagataaga
      1510       1520       1530       1540       1550       1560
agtaaactgg atacgttgcg tgatgaaatt cattcaatcc atcttgattc tgctgaagat
      1570       1580       1590       1600       1610       1620
ctaggattcg atccggacaa aaaactgaag ttggagaacc atcatctgca tggttggtgt
      1630       1640       1650       1660       1670       1680
atgaggttga cacgtaatga cgccaaggag ttacgtaaac ataagaagta cattgagttg
      1690       1700       1710       1720       1730       1740
tcgacagtaa aagctggtat attttttagt accaaacaat taaagtcaat cgccaatgaa
      1750       1760       1770       1780       1790       1800
accaatattc ttcaaaagga gtacgacaag caacaatcgg ctctggttag agaaattata
      1810       1820       1830       1840       1850       1860
aatattacat taacgtacac accagttttt gaaaaactat ccttagtctt agcgcattta
      1870       1880       1890       1900       1910       1920
gatgtgattg cctcttttgc tcatacttcc tcgtatgctc ctataccata cattagaccc
      1930       1940       1950       1960       1970       1980
aagttgcatc ccatggattc ggaaagaaga actcacctaa taagctcccg tcatccagta
      1990       2000       2010       2020       2030       2040
ctggaaatgc aagacgatat aagctttata tctaatgatg tcacattaga gagtggaaag
      2050       2060       2070       2080       2090       2100
ggcgactttt taatcataac tggaccaaac atgggaggta aatctactta catcagacag
      2110       2120       2130       2140       2150       2160
gttggtgtga tttctttaat ggcccaaatt ggttgtttcg taccttgtga agaagctgaa
      2170       2180       2190       2200       2210       2220
atagccatag tagatgcaat tctttgcagg gtcggggcag gagattccca attgaaaggt
      2230       2240       2250       2260       2270       2280
gtttccacat ttatggttga aatattggaa actgcttcta tactaaagaa tgcgagtaag
      2290       2300       2310       2320       2330       2340
aattctttga ttattgtaga tgaactaggg cgtggtacta gtacatatga tggttttggt
      2350       2360       2370       2380       2390       2400
ctagcttggg caattgctga acatatcgca agtaagattg gatgtttcgc tttgtttgca
      2410       2420       2430       2440       2450       2460
actcactttc atgaattgac agaattgtct gaaaaattgc ccaatgtcaa gaatatgcat
      2470       2480       2490       2500       2510       2520
gttgttgcac atatcgagaa aaatttaaaa gaacaaaaac atgacgatga ggacatcacg
      2530       2540       2550       2560       2570       2580
ttgttataca aagttgagcc tggtatttca gatcagtctt ttggtattca tgttgcagaa
      2590       2600       2610       2620       2630       2640
gttgttcaat ttccagaaaa aattgttaaa atggctaaac gtaaagccaa tgaattggac
      2650       2660       2670       2680       2690       2700
gatctaaaaa ctaataatga agatttgaaa aaagctaagc tatcattaca ggaagttaac
      2710       2720       2730       2740       2750       2760
gaaggtaata ttcgtttgaa ggctttactg aaagagtgga ttagaaaagt gaaggaggag
      2770       2780       2790       2800       2810       2820
ggtttacatg acccaagcaa aattactgaa gaagcttccc agcataaaat acaagagcta
      2830       2840       2850       2860       2870       2880
ttgcgtgcta tagcaaatga accagaaaag gaaaacgata attacctgaa atatataaaa
      2890
gccttgttgt tataa    

Last modification date: Oct. 2, 2011