Search Results

Overview

Uniprot IDP49959
Protein NameDouble-strand break repair protein MRE11
Gene NameMRE11
OrganismHomo sapiens

Kla Sites from experimental identification

Position Flanking peptide
416 GEEINFGKLITKPSE
510 RFRETRQKNTNEEDD
609 STRSRNSKTAVSASR
625 MSIIDAFKSTRQQPS
673 WSSTSSSKIMSQSQV

Function

Core component of the MRN complex, which plays a central role in double-strand break (DSB) repair, DNA recombination, maintenance of telomere integrity and meiosis (PubMed:11741547, PubMed:14657032, PubMed:22078559, PubMed:23080121, PubMed:24316220, PubMed:26240375, PubMed:27889449, PubMed:28867292, PubMed:29670289, PubMed:30464262, PubMed:30612738, PubMed:31353207, PubMed:37696958, PubMed:38128537, PubMed:9590181, PubMed:9651580, PubMed:9705271). The MRN complex is involved in the repair of DNA double-strand breaks (DSBs) via homologous recombination (HR), an error-free mechanism which primarily occurs during S and G2 phases (PubMed:24316220, PubMed:28867292, PubMed:31353207, PubMed:38128537). The complex (1) mediates the end resection of damaged DNA, which generates proper single-stranded DNA, a key initial steps in HR, and is (2) required for the recruitment of other repair factors and efficient activation of ATM and ATR upon DNA damage (PubMed:24316220, PubMed:27889449, PubMed:28867292, PubMed:36050397, PubMed:38128537). Within the MRN complex, MRE11 possesses both single-strand endonuclease activity and double-strand-specific 3'-5' exonuclease activity (PubMed:11741547, PubMed:22078559, PubMed:24316220, PubMed:26240375, PubMed:27889449, PubMed:29670289, PubMed:31353207, PubMed:36563124, PubMed:9590181, PubMed:9651580, PubMed:9705271). After DSBs, MRE11 is loaded onto DSBs sites and cleaves DNA by cooperating with RBBP8/CtIP to initiate end resection (PubMed:27814491, PubMed:27889449, PubMed:30787182). MRE11 first endonucleolytically cleaves the 5' strand at DNA DSB ends to prevent non-homologous end joining (NHEJ) and licence HR (PubMed:24316220). It then generates a single-stranded DNA gap via 3' to 5' exonucleolytic degradation to create entry sites for EXO1- and DNA2-mediated 5' to 3' long-range resection, which is required for single-strand invasion and recombination (PubMed:24316220, PubMed:28867292). RBBP8/CtIP specifically promotes the endonuclease activity of MRE11 to clear protein-DNA adducts and generate clean double-strand break ends (PubMed:27814491, PubMed:27889449, PubMed:30787182). MRE11 endonuclease activity is also enhanced by AGER/RAGE (By similarity). The MRN complex is also required for DNA damage signaling via activation of the ATM and ATR kinases: the nuclease activity of MRE11 is not required to activate ATM and ATR (PubMed:14657032, PubMed:15064416, PubMed:15790808, PubMed:16622404). The MRN complex is also required for the processing of R-loops (PubMed:31537797). The MRN complex is involved in the activation of the cGAS-STING pathway induced by DNA damage during tumorigenesis: the MRN complex acts by displacing CGAS from nucleosome sequestration, thereby activating it (By similarity). In telomeres the MRN complex may modulate t-loop formation (PubMed:10888888)

Protein Sequence

10 MSTADALDDE 20 NTFKILVATD 30 IHLGFMEKDA 40 VRGNDTFVTL 50 DEILRLAQEN 60 EVDFILLGGD 70 LFHENKPSRK 80 TLHTCLELLR 90 KYCMGDRPVQ 100 FEILSDQSVN 110 FGFSKFPWVN 120 YQDGNLNISI 130 PVFSIHGNHD 140 DPTGADALCA 150 LDILSCAGFV 160 NHFGRSMSVE 170 KIDISPVLLQ 180 KGSTKIALYG 190 LGSIPDERLY 200 RMFVNKKVTM 210 LRPKEDENSW 220 FNLFVIHQNR 230 SKHGSTNFIP 240 EQFLDDFIDL 250 VIWGHEHECK 260 IAPTKNEQQL 270 FYISQPGSSV 280 VTSLSPGEAV 290 KKHVGLLRIK 300 GRKMNMHKIP 310 LHTVRQFFME 320 DIVLANHPDI 330 FNPDNPKVTQ 340 AIQSFCLEKI 350 EEMLENAERE 360 RLGNSHQPEK 370 PLVRLRVDYS 380 GGFEPFSVLR 390 FSQKFVDRVA 400 NPKDIIHFFR 410 HREQKEKTGE 420 EINFGKLITK 430 PSEGTTLRVE 440 DLVKQYFQTA 450 EKNVQLSLLT 460 ERGMGEAVQE 470 FVDKEEKDAI 480 EELVKYQLEK 490 TQRFLKERHI 500 DALEDKIDEE 510 VRRFRETRQK 520 NTNEEDDEVR 530 EAMTRARALR 540 SQSEESASAF 550 SADDLMSIDL 560 AEQMANDSDD 570 SISAATNKGR 580 GRGRGRRGGR 590 GQNSASRGGS 600 QRGRADTGLE 610 TSTRSRNSKT 620 AVSASRNMSI 630 IDAFKSTRQQ 640 PSRNVTTKNY 650 SEVIEVDESD 660 VEEDIFPTTS 670 KTDQRWSSTS 680 SSKIMSQSQV 690 SKGVDFESSE 700 DDDDDPFMNT SSLRRNRR

Gene Ontology

Classification GO ID Description
Cellular Component GO:0098687 chromosomal region
Cellular Component GO:0000781 chromosome, telomeric region
Cellular Component GO:0005737 cytoplasm
Cellular Component GO:0005829 cytosol
Cellular Component GO:0030870 Mre11 complex
Cellular Component GO:0005654 nucleoplasm
Cellular Component GO:0005634 nucleus
Cellular Component GO:0016605 PML body
Cellular Component GO:0005657 replication fork
Cellular Component GO:0035861 site of double-strand break
Molecular Function GO:0008408 3'-5' exonuclease activity
Molecular Function GO:0008296 3'-5'-DNA exonuclease activity
Molecular Function GO:0045296 cadherin binding
Molecular Function GO:0004520 DNA endonuclease activity
Molecular Function GO:0003690 double-stranded DNA binding
Molecular Function GO:0042802 identical protein binding
Molecular Function GO:0030145 manganese ion binding
Molecular Function GO:0004518 nuclease activity
Molecular Function GO:0000014 single-stranded DNA endodeoxyribonuclease activity
Biological Process GO:0006974 DNA damage response
Biological Process GO:0000729 DNA double-strand break processing
Biological Process GO:0006310 DNA recombination
Biological Process GO:0006281 DNA repair
Biological Process GO:0110025 DNA strand resection involved in replication fork processing
Biological Process GO:0006302 double-strand break repair
Biological Process GO:0000724 double-strand break repair via homologous recombination
Biological Process GO:0006303 double-strand break repair via nonhomologous end joining
Biological Process GO:0035825 homologous recombination
Biological Process GO:0042138 meiotic DNA double-strand break formation
Biological Process GO:0097552 mitochondrial double-strand break repair via homologous recombination
Biological Process GO:0007095 mitotic G2 DNA damage checkpoint signaling
Biological Process GO:0044818 mitotic G2/M transition checkpoint
Biological Process GO:0031573 mitotic intra-S DNA damage checkpoint signaling
Biological Process GO:0043066 negative regulation of apoptotic process
Biological Process GO:2001033 negative regulation of double-strand break repair via nonhomologous end joining
Biological Process GO:2000781 positive regulation of double-strand break repair
Biological Process GO:0032206 positive regulation of telomere maintenance
Biological Process GO:0062176 R-loop processing
Biological Process GO:0007131 reciprocal meiotic recombination
Biological Process GO:0000019 regulation of mitotic recombination
Biological Process GO:0007062 sister chromatid cohesion
Biological Process GO:0000723 telomere maintenance
Biological Process GO:0007004 telomere maintenance via telomerase
Biological Process GO:0031860 telomeric 3' overhang formation

Reference

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[2] Hong H, Chen X, Wang H, Gu X, Yuan Y et al.. Global profiling of protein lysine lactylation and potential target modified protein analysis in hepatocellular carcinoma.. Proteomics 23(9):e2200432. 2023 May. PMID: 36625413.

[3] He C, Zhang J, Bai X, Lu C, Zhang K. Lysine lactylation-based insight to understanding the characterization of cervical cancer.. Biochim Biophys Acta Mol Basis Dis 1870(7):167356. 2024 Oct. PMID: 39025375.

[4] Guo X, Ren X, Yan C, Huang H. Quantitative Proteomics Reveals the Role of Lysine Lactylation in Lenalidomide-Resistance in Multiple Myeloma Cells.. ACS Chem Biol 20(7):1728-1738. 2025 Jul 18. PMID: 40590393.

[5] He J, Lai T, Zhou Z, Yang H, Lei Z et al.. Multiomics profiling reveals the involvement of protein lactylation in nonhomologous end joining pathway conferring radioresistance in lung adenocarcinoma cell.. Sci Rep 15(1):24651. 2025 Jul 9. PMID: 40634431.

[6] Wu Q, Li Z, Gong T, Zheng X, Zhou X et al.. Porphyromonas gingivalis infection induces lysine lactylation reprogramming in human umbilical vein endothelial cells.. Front Cell Infect Microbiol 16:1706727. 2026. PMID: 41696360.