REPAIRtoire - a database of DNA repair pathways

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Mlh1

Protein FULL name:

MutL protein homolog 1 [Mus musculus].


Mlh1 (Mus musculus) is product of expression of Mlh1 gene.






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-Msh6) 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).

SUBUNIT: Heterodimer of Mlh1 and Pms2 (MutL alpha), Mlh1 and Pms1 (MutL beta) or Mlh1 and Mlh3 (MutL gamma). Forms a ternary complex with MutS alpha (Msh2-Msh6) or MutS beta (Msh2-Msh3). Part of the BRCA1-associated genome surveillance complex (BASC), which contains BRCA1, Msh2, Msh6, Mlh1, Atm, Blm, Pms2 and the RAD50- MRE11-NBS1 protein complex. This association could be a dynamic process changing throughout the cell cycle and within subnuclear domains. Interacts with MBD4. Interacts with EXO1 (By similarity).

SUBCELLULAR LOCATION: Nucleus (By similarity).

SIMILARITY: Belongs to the DNA mismatch repair mutL/hexB family.


NCBI GenPept GI number(s): 19387852
Species: Mus musculus

Links to other databases:

Database ID Link
Uniprot Q9JK91 Q9JK91
PFAM: - Q9JK91 (Link - using uniprot id)
InterPro: - Q9JK91 (Link - using uniprot id)
CATH: - -
SCOP: - -
PDB: - -


Protein sequence:
MAFVAGVIRRLDETVVNRIAAGEVIQRPANAIKEMIENCLDAKSTNIQVV
VKEGGLKLIQIQDNGTGIRKEDLDIVCERFTTSKLQTFEDLASISTYGFR
GEALASISHVAHVTITTKTADGKCAYRASYSDGKLQAPPKPCAGNQGTLI
TVEDLFYNIITRRKALKNPSEEYGKILEVVGRYSIHNSGISISVKKQGET
VSDVRTLPNATTVDNIRSIFGNAVSRELIEVGCEDKTLAFKMNGYISNAN
YSVKKCIFLLFINHRLVESAALRKAIETVYAAYLPKNTHPFLYLSLEISP
QNVDVNVHPTKHEVHFLHEESILQRVQQHIESKLLGSNSSRMYFTQTLLP
GLAGPSGEAARPTTGVASSSTSGSGDKVYAYQMVRTDSRDQKLDAFLQPV
SSLVPSQPQDPAPVRGARTEGSPERATREDEEMLALPAPAEAAAESENLE
RESLMETSDTAQKAAPTSSPGSSRKRHREDSDVEMVENASGKEMTAACYP
RRRIINLTSVLSLQEEISERCHETLREMLRNHSFVGCVNPQWALAQHQTK
LYLLNTTKLSEELFYQILIYDFANFGVLRLSEPAPLFDLAMLALDSPESG
WTEDDGPKEGLAEYIVEFLKKKAEMLADYFSVEIDEEGNLIGLPLLIDSY
VPPLEGLPIFILRLATEVNWDEEKECFESLSKECAMFYSIRKQYILEEST
LSGQQSDMPGSTSKPWKWTVEHIIYKAFRSHLLPPKHFTEDGNVLQLANL
PDLYKVFERC

Mlh1 (Mus musculus) belongs to following protein families:
References:

Title Authors Journal
Meiotic pachytene arrest in MLH1-deficient mice. Edelmann W, Cohen PE, Kane M, Lau K, Morrow B, Bennett S, Umar A, Kunkel T, Cattoretti G, Chaganti R, Pollard JW, Kolodner RD, Kucherlapati R Cell June 28, 1996


Last modification of this entry: Oct. 6, 2010.

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