Protein: Bifunctional 3'-5' exonuclease/ATP-dependent helicase WRN (Werner syndrome protein homolog) [Includes: 3'-5' exonuclease (EC 3.1.-.-); ATP-dependent helicase (EC 5.6.2.4) (DNA 3'-5' helicase WRN)] (O09053)
Organism: Mus musculus (Mouse)
Function: Multifunctional enzyme that has both magnesium and ATP-dependent DNA-helicase activity and 3'->5' exonuclease activity towards double-stranded DNA with a 5'-overhang. Has no nuclease activity towards single-stranded DNA or blunt-ended double-stranded DNA. Binds preferentially to DNA substrates containing alternate secondary structures, such as replication forks and Holliday junctions. May play an important role in the dissociation of joint DNA molecules that can arise as products of homologous recombination, at stalled replication forks or during DNA repair. Alleviates stalling of DNA polymerases at the site of DNA lesions. Important for genomic integrity. Plays a role in the formation of DNA replication focal centers; stably associates with foci elements generating binding sites for RP-A (By similarity). Plays a role in double-strand break repair after gamma-irradiation (By similarity).
Subcellular location: Nucleus, nucleolus {ECO:0000250|UniProtKB:Q14191}. Nucleus {ECO:0000269|PubMed:9618508}. Nucleus, nucleoplasm {ECO:0000250|UniProtKB:Q14191}. Chromosome {ECO:0000250|UniProtKB:Q14191}. Note=Gamma-irradiation leads to its translocation from nucleoli to nucleoplasm and PML regulates the irradiation-induced WRN relocation. Localizes to DNA damage sites. {ECO:0000250|UniProtKB:Q14191}.
Interaction partners:
- DNA replication ATP-dependent helicase/nuclease DNA2
- Flap endonuclease 1
- X-ray repair cross-complementing protein 6
- DNA repair protein RAD52 homolog
- X-ray repair cross-complementing protein 5
- Exonuclease 1
- Fanconi anemia group M protein homolog
- Replication protein A 70 kDa DNA-binding subunit
- Replication protein A 14 kDa subunit
- DNA topoisomerase 3-alpha
Sequence:
METTSLQRKFPEWMSMQSQRCATEEKACVQKSVLEDNLPFLEFPGSIVYSYEASDCSFLSEDISMRLSDGDVVGFDMEWPPIYKPGKRSRVAVIQLCVSESKCYLFHISSMSVFPQGLKMLLENKSIKKAGVGIEGDQWKLLRDFDVKLESFVELTDVANEKLKCAETWSLNGLVKHVLGKQLLKDKSIRCSNWSNFPLTEDQKLYAATDAYAGLIIYQKLGNLGDTAQVFALNKAEENLPLEMKKQLNSISEEMRDLANRFPVTCRNLETLQRVPVILKSISENLCSLRKVICGPTNTETRLKPGSSFNLLSSEDSAAAGEKEKQIGKHSTFAKIKEEPWDPELDSLVKQEEVDVFRNQVKQEKGESENEIEDNLLREDMERTCVIPSISENELQDLEQQAKEEKYNDVSHQLSEHLSPNDDENDSSYIIESDEDLEMEMLKSLENLNSDVVEPTHSTWLEMGTNGRLPPEEEDGHGNEAIKEEQEEEDHLLPEPNAKQINCLKTYFGHSSFKPVQWKVIHSVLEERRDNVVVMATGYGKSLCFQYPPVYTGKIGIVISPLISLMEDQVLQLELSNVPACLLGSAQSKNILGDVKLGKYRVIYITPEFCSGNLDLLQQLDSSIGITLIAVDEAHCISEWGHDFRSSFRMLGSLKTALPLVPVIALSATASSSIREDIISCLNLKDPQITCTGFDRPNLYLEVGRKTGNILQDLKPFLVRKASSAWEFEGPTIIYCPSRKMTEQVTAELGKLNLACRTYHAGMKISERKDVHHRFLRDEIQCVVATVAFGMGINKADIRKVIHYGAPKEMESYYQEIGRAGRDGLQSSCHLLWAPADFNTSRNLLIEIHDEKFRLYKLKMMVKMEKYLHSSQCRRRIILSHFEDKCLQKASLDIMGTEKCCDNCRPRLNHCLTANNSEDASQDFGPQAFQLLSAVDILQEKFGIGIPILFLRGSNSQRLPDKYRGHRLFGAGKEQAESWWKTLSHHLIAEGFLVEVPKENKYIKTCSLTKKGRKWLGEASSQSPPSLLLQANEEMFPRKVLLPSSNPVSPETTQHSSNQNPAGLTTKQSNLERTHSYKVPEKVSSGTNIPKKSAVMPSPGTSSSPLEPAISAQELDARTGLYARLVEARQKHANKMDVPPAILATNKVLLDMAKMRPTTVENMKQIDGVSEGKAALLAPLLEVIKHFCQVTSVQTDLLSSAKPHKEQEKSQEMEKKDCSLPQSVAVTYTLFQEKKMPLHSIAENRLLPLTAAGMHLAQAVKAGYPLDMERAGLTPETWKIIMDVIRNPPINSDMYKVKLIRMLVPENLDTYLIHMAIEILQSGSDSRTQPPCDSSRKRRFPSSAESCESCKESKEAVTETKASSSESKRKLPEWFAKGNVPSADTGSSSSMAKTKKKGLFS