3.1.99.B1	evolution	RNase H belongs to the eukaryotic Mre11/Rad50 (MR) and bacterial SbcCD complex family. The crystal structure of T4 RNase H shows a close homology to flap endonucleases of the FEN-1 family rather than RNase H family. FEN-1 is a family of structure-specific 5'-nucleases, which is conserved from bacteriophage to humans	751635	
3.1.99.B1	malfunction	the enzyme has important roles in DNA replication, repair, and recombination	-, 745273	
3.1.99.B1	malfunction	the V43I substitution increases the ratio between exonuclease (EC 3.1.13.2) and endonuclease (EC 3.1.99.) activities of RNase H whereas L242I substitution does not affect the nuclease activity of RNase H in vitro. The Das13 mutant of RNase H has substitutions of valine 43 and leucine 242 with isoleucines. Both mutations are necessary for the full das mutant effect in vivo. The V43I substitution may lead to disposition of H4 helix, responsible for the interaction with the first base pairs of 5' end of branched DNA. These structural changes may affect unwinding of the first base pairs of gapped or nicked DNA generating a short flap and therefore may stabilize the DNA-enzyme complex. The L242I substitution does not affect the structure of RNase H and its role in providing the das-effect remains unclear	751635	
3.1.99.B1	metabolism	plays important roles with DNA polymerases in DNA replication, repair and recombination	-, 744854	
3.1.99.B1	additional information	mixed quantum-classical (QM/MM) metadynamics and umbrella sampling free energy calculations are employed on a reconstructed reactive hFEN/double strand (ds) DNA adduct for an atomistic and energetic rendering of the enzymatic catalysis promoted by the human FEN1, structure-function analysis, overview. The enzymatic phosphate hydrolysis proceeds as an SN2-like nucleophilic attack on the scissile phosphate performed by an hydroxide ion, which is typically formed upon water activation	749449	
3.1.99.B1	additional information	molecular modelling of the nuclease structure, and modeling of the function of flap endonucleases	751635	
3.1.99.B1	physiological function	Flap endonucleases (FENs) are nucleic acid hydrolyzing enzymes in charge of excising 5'-small DNA and RNA fragments (flaps) protruding from nucleic acid structures during the lagging strand DNA replication or the longpatch base excision repair (LP-BER) processes. Important role of FENs in maintaining nucleic acid fidelity and cell proliferation, high levels of FEN1 are believed to support cancer cell hyperproliferation	749449	
3.1.99.B1	physiological function	RNase H is a 5'-nuclease required to remove RNA primers from lagging strand fragments during DNA replication. It forms the gp46/47 enzyme complex consists of a DNA-activated ATPase, an ssDNA endonuclease and a 3'-5' dsDNA exonuclease	751635	
3.1.99.B1	physiological function	the structure-specific nuclease is involved in DNA replication and repair. In DNA replication the enzyme removes the RNA primer of the lagging strand synthesis. In DNA repair, FEN-1 eliminates the damaged DNA and maintains genome integrity by preventing repeat sequence expansion. It recognizes branched structures containing single unpaired ssDNA (flap). Both the 3'-flap and 5'-flap are recognized by the enzyme and the 5'-flap region is excised. The product is a nicked duplex, which is subsequently sealed by DNA ligase	720576