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MLH1

Gene
mlh1
Protein
DNA mismatch repair protein Mlh1
Organism
Dictyostelium discoideum
Length
884 amino acids
Function
Heterodimerizes with pms1 to form MutL alpha, a component of the post-replicative DNA mismatch repair system (MMR). DNA repair is initiated by MutS alpha (msh2-msh6) or MutS beta (msh2-msh3) binding to a dsDNA mismatch, then MutL alpha is recruited to the heteroduplex. Assembly of the MutL-MutS-heteroduplex ternary complex in presence of rfc and pcna is sufficient to activate endonuclease activity of pms1. It introduces single-strand breaks near the mismatch and thus generates new entry points for the exonuclease exo1 to degrade the strand containing the mismatch (By similarity).
Similarity
Belongs to the DNA mismatch repair MutL/HexB family.
Mass
98.753 kDa
Sequence
MDFLKSLPPLQTTDSNSTTAAVNTTTTTATNTATTTATNTATTTTTTTTTNLNNLINESKKKIHRLTQEVVNKISAGEVIQRPSNALKELLENCLDAKSTTITVTVKDGGMKFLQIQDNGSGIRLEDMGIVCERFTTSKLTKFEDLRSIQSFGFRGEALSSISHVSHLKILTKTADSPCAYRACYLNGKLTPPSPNEQSSDPKPCAGVNGTQITVEDLFFNTPSRKNVLKNTVDEHSRIVLLMKKYAINNPTVSFILKKQGDPTPEVHTSGGQNSLEKDVIGSLYGTDLSKELKIITIDPNNPNPNNDDDDNISGSQIKNSNLNRLDFTMKGFFSSTNYNSKKINFILFINGRLVDSKNLKTGLEQVYSKYLPKGTHPFMFIRLLVPPKNIDVNIHPTKSEVKILHEEQIIEFIQQKVDQELSISSNSKTFSTQILLPGFDQDNVSSSQKKQKNSQSSSTQTKSTNNNNNPTSRKEPIEYAKDKIRSDSKSQTLDAFLNPMDYNNNNDSSIDDNDGSGIGRYDDVDGSAGAAGAGGKFNDNLIFNDNSENEAPRDIDNPLSSVTPIKSKEQRQQQSTTTTTTTTTTTATTKSNSPASKNDIKKLQEHTFITPRKTRKYKQVELTSIKTLISEFQSNVHDGLKEFFNDCVFVGCLDHSYALVQFGKKLYLINLENITKELFYQLSLLRFSDFDSIKFSQSLSIYSLLLVSLDSPLSGWMESDGPKDKIADYLTKLLISKKELLNEYFSIEINEDGELVGIPQVLDHYVPCTDNLPIFLLKLATEVEWEFEKECFAGIVKEISSFFKIEPSFLKLRDTQVNNQQQTNSTTTTNNINFIKKDGKEWIIQHLIFPAFRKLSPPKKFANDGSVIQITTLDNLYKVFERC

Gene
MLH1
Protein
DNA mismatch repair protein MLH1
Organism
Saccharomyces cerevisiae (strain ATCC 204508 / S288c)
Length
769 amino acids
Function
Required for DNA mismatch repair (MMR), correcting base-base mismatches and insertion-deletion loops (IDLs) resulting from DNA replication, DNA damage or from recombination events between non-identical sequences during meiosis. Component of different MutL heterodimers that form a ternary complex with the MutS heterodimers, which initially recognize the DNA mismatches. This complex is thought to be responsible for directing the downsteam MMR events, including strand discrimination, excision, and resynthesis. Plays a major role in maintaining the genetic stability of simple sequence repeats, the repair of heteroduplex sites present in meiotic recombination intermediates, and the promotion of meiotic crossing-over.
Similarity
Belongs to the DNA mismatch repair MutL/HexB family.
Mass
87.062 kDa
Sequence
MSLRIKALDASVVNKIAAGEIIISPVNALKEMMENSIDANATMIDILVKEGGIKVLQITDNGSGINKADLPILCERFTTSKLQKFEDLSQIQTYGFRGEALASISHVARVTVTTKVKEDRCAWRVSYAEGKMLESPKPVAGKDGTTILVEDLFFNIPSRLRALRSHNDEYSKILDVVGRYAIHSKDIGFSCKKFGDSNYSLSVKPSYTVQDRIRTVFNKSVASNLITFHISKVEDLNLESVDGKVCNLNFISKKSISPIFFINNRLVTCDLLRRALNSVYSNYLPKGNRPFIYLGIVIDPAAVDVNVHPTKREVRFLSQDEIIEKIANQLHAELSAIDTSRTFKASSISTNKPESLIPFNDTIESDRNRKSLRQAQVVENSYTTANSQLRKAKRQENKLVRIDASQAKITSFLSSSQQFNFEGSSTKRQLSEPKVTNVSHSQEAEKLTLNESEQPRDANTINDNDLKDQPKKKQKLGDYKVPSIADDEKNALPISKDGYIRVPKERVNVNLTSIKKLREKVDDSIHRELTDIFANLNYVGVVDEERRLAAIQHDLKLFLIDYGSVCYELFYQIGLTDFANFGKINLQSTNVSDDIVLYNLLSEFDELNDDASKEKIISKIWDMSSMLNEYYSIELVNDGLDNDLKSVKLKSLPLLLKGYIPSLVKLPFFIYRLGKEVDWEDEQECLDGILREIALLYIPDMVPKVDTSDASLSEDEKAQFINRKEHISSLLEHVLFPCIKRRFLAPRHILKDVVEIANLPDLYKVFERC

Gene
Mlh1
Protein
DNA mismatch repair protein Mlh1
Organism
Mus musculus
Length
760 amino acids
Function
Heterodimerizes with Pms2 to form MutL alpha, a component of the post-replicative DNA mismatch repair system (MMR). DNA repair is initiated by MutS alpha (Msh2-Msh6) or MutS beta (MSH2-MSH3) binding to a dsDNA mismatch, then MutL alpha is recruited to the heteroduplex. Assembly of the MutL-MutS-heteroduplex ternary complex in presence of RFC and PCNA is sufficient to activate endonuclease activity of Pms2. It introduces single-strand breaks near the mismatch and thus generates new entry points for the exonuclease EXO1 to degrade the strand containing the mismatch. DNA methylation would prevent cleavage and therefore assure that only the newly mutated DNA strand is going to be corrected. MutL alpha (Mlh1-Pms2) interacts physically with the clamp loader subunits of DNA polymerase III, suggesting that it may play a role to recruit the DNA polymerase III to the site of the MMR. Also implicated in DNA damage signaling, a process which induces cell cycle arrest and can lead to apoptosis in case of major DNA damages. Heterodimerizes with Mlh3 to form MutL gamma which plays a role in meiosis (By similarity).
Similarity
Belongs to the DNA mismatch repair MutL/HexB family.
Mass
84.67 kDa
Sequence
MAFVAGVIRRLDETVVNRIAAGEVIQRPANAIKEMIENCLDAKSTNIQVVVKEGGLKLIQIQDNGTGIRKEDLDIVCERFTTSKLQTFEDLASISTYGFRGEALASISHVAHVTITTKTADGKCAYRASYSDGKLQAPPKPCAGNQGTLITVEDLFYNIITRRKALKNPSEEYGKILEVVGRYSIHNSGISFSVKKQGETVSDVRTLPNATTVDNIRSIFGNAVSRELIEVGCEDKTLAFKMNGYISNANYSVKKCIFLLFINHRLVESAALRKAIETVYAAYLPKNTHPFLYLSLEISPQNVDVNVHPTKHEVHFLHEESILQRVQQHIESKLLGSNSSRMYFTQTLLPGLAGPSGEAARPTTGVASSSTSGSGDKVYAYQMVRTDSREQKLDAFLQPVSSLGPSQPQDPAPVRGARTEGSPERATREDEEMLALPAPAEAAAESENLERESLMETSDAAQKAAPTSSPGSSRKRHREDSDVEMVENASGKEMTAACYPRRRIINLTSVLSLQEEISERCHETLREMLRNHSFVGCVNPQWALAQHQTKLYLLNTTKLSEELFYQILIYDFANFGVLRLSEPAPLFDLAMLALDSPESGWTEDDGPKEGLAEYIVEFLKKKAEMLADYFSVEIDEEGNLIGLPLLIDSYVPPLEGLPIFILRLATEVNWDEEKECFESLSKECAMFYSIRKQYILEESTLSGQQSDMPGSTSKPWKWTVEHIIYKAFRSHLLPPKHFTEDGNVLQLANLPDLYKVFERC

Gene
Mlh1
Protein
DNA mismatch repair protein Mlh1
Organism
Rattus norvegicus
Length
757 amino acids
Function
Heterodimerizes with Pms2 to form MutL alpha, a component of the post-replicative DNA mismatch repair system (MMR). DNA repair is initiated by MutS alpha (Msh2-Msh6) or MutS beta (MSH2-MSH3) binding to a dsDNA mismatch, then MutL alpha is recruited to the heteroduplex. Assembly of the MutL-MutS-heteroduplex ternary complex in presence of RFC and PCNA is sufficient to activate endonuclease activity of Pms2. It introduces single-strand breaks near the mismatch and thus generates new entry points for the exonuclease EXO1 to degrade the strand containing the mismatch. DNA methylation would prevent cleavage and therefore assure that only the newly mutated DNA strand is going to be corrected. MutL alpha (Mlh1-Pms2) interacts physically with the clamp loader subunits of DNA polymerase III, suggesting that it may play a role to recruit the DNA polymerase III to the site of the MMR. Also implicated in DNA damage signaling, a process which induces cell cycle arrest and can lead to apoptosis in case of major DNA damages. Heterodimerizes with Mlh3 to form MutL gamma which plays a role in meiosis (By similarity).
Similarity
Belongs to the DNA mismatch repair MutL/HexB family.
Mass
84.54 kDa
Sequence
MSFVAGVIRRLDETVVNRIAAGEVIQRPANAIKEMTENCLDAKSTNIQVIVREGGLKLIQIQDNGTGIRKEDLDIVCERFTTSKLQTFEDLAMISTYGFRGEALASISHVAHVTITTKTADGKCAYRASYSDGKLQAPPKPCAGNQGTLITVEDLFYNIITRKKALKNPSEEYGKILEVVGRYSIHNSGISFSVKKQGETVSDVRTLPNATTVDNIRSIFGNAVSRELIEVGCEDKTLAFKMNGYISNANYSVKKCIFLLFINHRLVESAALKKAIEAVYAAYLPKNTHPFLYLILEISPQNVDVNVHPTKHEVHFLHEESILERVQQHIESKLLGSNSSRMYFTQTLLPGLAGPSGEAVKSTTGIASSSTSGSGDKVHAYQMVRTDSRDQKLDAFMQPVSRRLPSQPQDPVPGNRTEGSPEKAMQKDQEISELPAPMEAAADSASLERESVIGASEVVAPQRHPSSPGSSRKRHPEDSDVEMMENDSRKEMTAACYPRRRIINLTSVLSLQEEINDRGHETLREMLRNHTFVGCVNPQWALAQHQTKLYLLNTTKLSEELFYQILIYDFANFGVLRLPEPAPLFDFAMLALDSPESGWTEEDGPKEGLAEYIVEFLKKKAKMLADYFSVEIDEEGNLIGLPLLIDSYVPPLEGLPIFILRLATEVNWDEEECFESLSKECAVFYSIRKQYILEESALSGQQSDMPGSPSKPWKWTVEHIIYKAFRSHLLPPKHFTEDGNVLQLANLPDLCKVFERC

Gene
MLH1
Protein
DNA mismatch repair protein Mlh1
Organism
Homo sapiens
Length
756 amino acids
Function
Heterodimerizes with PMS2 to form MutL alpha, a component of the post-replicative DNA mismatch repair system (MMR). DNA repair is initiated by MutS alpha (MSH2-MSH6) or MutS beta (MSH2-MSH3) binding to a dsDNA mismatch, then MutL alpha is recruited to the heteroduplex. Assembly of the MutL-MutS-heteroduplex ternary complex in presence of RFC and PCNA is sufficient to activate endonuclease activity of PMS2. It introduces single-strand breaks near the mismatch and thus generates new entry points for the exonuclease EXO1 to degrade the strand containing the mismatch. DNA methylation would prevent cleavage and therefore assure that only the newly mutated DNA strand is going to be corrected. MutL alpha (MLH1-PMS2) interacts physically with the clamp loader subunits of DNA polymerase III, suggesting that it may play a role to recruit the DNA polymerase III to the site of the MMR. Also implicated in DNA damage signaling, a process which induces cell cycle arrest and can lead to apoptosis in case of major DNA damages. Heterodimerizes with MLH3 to form MutL gamma which plays a role in meiosis.
Similarity
Belongs to the DNA mismatch repair MutL/HexB family.
Mass
84.601 kDa
Sequence
MSFVAGVIRRLDETVVNRIAAGEVIQRPANAIKEMIENCLDAKSTSIQVIVKEGGLKLIQIQDNGTGIRKEDLDIVCERFTTSKLQSFEDLASISTYGFRGEALASISHVAHVTITTKTADGKCAYRASYSDGKLKAPPKPCAGNQGTQITVEDLFYNIATRRKALKNPSEEYGKILEVVGRYSVHNAGISFSVKKQGETVADVRTLPNASTVDNIRSIFGNAVSRELIEIGCEDKTLAFKMNGYISNANYSVKKCIFLLFINHRLVESTSLRKAIETVYAAYLPKNTHPFLYLSLEISPQNVDVNVHPTKHEVHFLHEESILERVQQHIESKLLGSNSSRMYFTQTLLPGLAGPSGEMVKSTTSLTSSSTSGSSDKVYAHQMVRTDSREQKLDAFLQPLSKPLSSQPQAIVTEDKTDISSGRARQQDEEMLELPAPAEVAAKNQSLEGDTTKGTSEMSEKRGPTSSNPRKRHREDSDVEMVEDDSRKEMTAACTPRRRIINLTSVLSLQEEINEQGHEVLREMLHNHSFVGCVNPQWALAQHQTKLYLLNTTKLSEELFYQILIYDFANFGVLRLSEPAPLFDLAMLALDSPESGWTEEDGPKEGLAEYIVEFLKKKAEMLADYFSLEIDEEGNLIGLPLLIDNYVPPLEGLPIFILRLATEVNWDEEKECFESLSKECAMFYSIRKQYISEESTLSGQQSEVPGSIPNSWKWTVEHIVYKALRSHILPPKHFTEDGNILQLANLPDLYKVFERC

Gene
MLH1
Protein
DNA mismatch repair protein MLH1
Organism
Arabidopsis thaliana
Length
737 amino acids
Function
Involved in DNA mismatch repair (MMR), correcting insertion-deletion loops (IDLs) resulting from DNA replication, DNA damage or from recombination events between non-identical sequences during meiosis. Component of the MutLbeta heterodimer, which probably forms a ternary complex with the MutSbeta heterodimer that initially recognizes the DNA mismatches. This complex is thought to be responsible for directing the downsteam MMR events, including strand discrimination, excision, and resynthesis. Plays a major role in promoting meiotic crossing-over and is involved in maintaining the genetic stability of simple sequence repeats by correction of frameshift intermediates.
Similarity
Belongs to the DNA mismatch repair MutL/HexB family.
Mass
82.365 kDa
Sequence
MIDDSSLTAEMEEEESPATTIVPREPPKIQRLEESVVNRIAAGEVIQRPVSAVKELVENSLDADSSSISVVVKDGGLKLIQVSDDGHGIRREDLPILCERHTTSKLTKFEDLFSLSSMGFRGEALASMTYVAHVTVTTITKGQIHGYRVSYRDGVMEHEPKACAAVKGTQIMVENLFYNMIARRKTLQNSADDYGKIVDLLSRMAIHYNNVSFSCRKHGAVKADVHSVVSPSRLDSIRSVYGVSVAKNLMKVEVSSCDSSGCTFDMEGFISNSNYVAKKTILVLFINDRLVECSALKRAIEIVYAATLPKASKPFVYMSINLPREHVDINIHPTKKEVSLLNQEIIIEMIQSEVEVKLRNANDTRTFQEQKVEYIQSTLTSQKSDSPVSQKPSGQKTQKVPVNKMVRTDSSDPAGRLHAFLQPKPQSLPDKVSSLSVVRSSVRQRRNPKETADLSSVQELIAGVDSCCHPGMLETVRNCTYVGMADDVFALVQYNTHLYLANVVNLSKELMYQQTLRRFAHFNAIQLSDPAPLSELILLALKEEDLDPGNDTKDDLKERIAEMNTELLKEKAEMLEEYFSVHIDSSANLSRLPVILDQYTPDMDRVPEFLLCLGNDVEWEDEKSCFQGVSAAIGNFYAMHPPLLPNPSGDGIQFYSKRGESSQEKSDLEGNVDMEDNLDQDLLSDAENAWAQREWSIQHVLFPSMRLFLKPPASMASNGTFVKVASLEKLYKIFERC

Gene
mlh1
Protein
Putative MutL protein homolog 1
Organism
Schizosaccharomyces pombe (strain 972 / ATCC 24843)
Length
684 amino acids
Function
This protein is involved in the repair of mismatches in DNA.
Similarity
Belongs to the DNA mismatch repair MutL/HexB family.
Mass
77.254 kDa
Sequence
MDVNSRAKIRPLDQLVINKIAAGEIIERPENAIKELIENSLDAGSTSIDVLLKDGGLKLLQITDNGSGIQYDDLPYLCQRFSTSKIDNFNDLQHLQTFGFRGEALASISHVAKVTVVTKLSSDIHAWKAFYVDGALAPISPGMSPAPQPCAGKQGTVITAEDLFYNVRSRKSALKNGSEEFRRIMILVQKYAIHNDQVSFNCKKVGDTVASLSLSSRLSKADKIRHIYGPRVASHLRDFSLGEGQSSIVGFSANGFISNADFQDKKSNLILFINNRLVESVELRHALEETYAKYLHKGASYFVYLSLNMSPEQLDVNVHPSKRIVHFLYDQEIATSICDKLGEILERTDTERSYPLQAMIPSISNTKNAESSSQKAVRTYENYLVRTDPRERSIKSMLSDNFLQRSSNNYDNEIIEKVDSANSNKNATNDIKDLQTEEIVEEGNSIDLESIKSLQKQVINSMHVLATNILTEHKYVGLVCPTRRIAAVQHNIGLYVVDYGKLSYHLFYQICLTEFGNYGEFVLETPLSISDLFEIVNGDEDKSESEKFTRLLVSRRDMLKDYFSISVTSGGLLTAVPMLSPKYHPPFEQLPLLISSLTPKFFDWLDEKSCLNGIMKAIAKFYVPLPLSYEESDVKSIRSLESCLEDYLFPEFRRRVICPKKVFEEKCIYQITSLPRLYNVFERC