This is the very N-terminal region of chordate RecQ-like DNA helicase BLM proteins. BLM participates in DNA replication and repair [, , , , ]. This domain, together with , may play a role in regulation and oligomerization of BLM. These domains are also important in mediating interactions with partner proteins [].
This is a C-terminal domain in RecQ-like DNA helicase BLM subfamily []. The helicase participates in DNA replication and repair, exhibiting a magnesium-dependent ATP-dependent DNA-helicase activity that unwinds single- and double-stranded DNA in a 3'-5' direction.
This entry represents the N-terminal OB-fold domain of RMI (RecQ-mediated genome instability protein) proteins []. This domain forms a stable complex with Bloom syndrome protein BLM and DNA topoisomerase 3-alpha [].
This entry represents the N-terminal domain of RMI1 (RecQ-mediated genome instability protein 1) and similar proteins []. This domain carries an oligo-nucleotide-binding domain or OB-fold, and forms a stable complex with Bloom syndrome protein BLM and DNA topoisomerase 3-alpha [].
This domain is found on RecQ-like DNA helicase BLM in higher eukaryotes []. It lies between the BDHCT (), and DEAD-box domains (). This domain, together with , may play a role in regulation and oligomerization of BLM. These domains are also important in mediating interactions with partner proteins [].
This entry represents the N-terminal helical domain of RMI 1 (RecQ-mediated genome instability protein) proteins from metazoa []. This domain is found at the N-terminal of an oligo-nucleotide-binding domain or OB-fold, and forms a stable complex with Bloom syndrome protein BLM and DNA topoisomerase 3-alpha [, ].
This entry represents the N-terminal helical domain of RMI 1 (RecQ-mediated genome instability protein 1) and similar proteins []. This domain is found at the N-terminal of an oligo-nucleotide-binding domain or OB-fold, and forms a stable complex with Bloom syndrome protein BLM and DNA topoisomerase 3-alpha [, ].
Bleomycin (Blm) is a glycopeptide antibiotic produced naturally by actinomycetes. It is a strong DNA-cutting agent and thus finds use as a potent anti-cancer drug. The DNA-cutting mechanism is complex, involving concomitant oxidation of FeII and reduction of oxygen. Inaddition to iron, Blm binds other transition metals: cobalt, nickel, copper and zinc. Actinomycetes have developed a defence mechanism against this lethal compound, producing a protein that confers resistance to Blm through drug sequestering.The crystal structure of the bleomycin resistance protein reveals 2identically-folded halves, each having an alpha/beta fold but showing nosequence similarity []. Each half comprises a 4-stranded β-sheet anda short α-helix (3 turns). The sheets within each half lie roughly atright-angles and are related by an approximate 2-fold axis. The crystalpacking shows compact dimers that have a hydrophobic interface and areinvolved in mutual chain exchange.
The HRDC (helicase and RNaseD C-terminal) domain is comprised of two orthogonally packed α-hairpin subdomains, and is involved in interactions with DNA and protein. It has been suggested that this domain plays a role dissolving double Holliday junctions efficiently [].HRDC domains are found at the C terminus of many RecQ helicases, including the human Bifunctional 3'-5' exonuclease/ATP-dependent helicase WRN and RecQ-like DNA helicase BLM [, ]. RecQ helicases have been shown to unwind DNA in an ATP-dependent manner. The structure of the HRDC domain consists of a 4-5 helical bundle of two orthogonally packed alpha-hairpins, and as such it resembles auxiliary domains in bacterial DNA helicases and other proteins that interact with nucleic acids. A positively charged region on the surface of the HRDC domain is able to interact with DNA.The HRDC domain is also present in eukaryotic and archaeal RNA polymerase II subunit RBP4, the N-terminal of which forms a heterodimerisation α-hairpin [, ].The HRDC domain has a putative role in nucleic acid binding. Mutations in the HRDC domain associated with the human BLM gene result in Bloom Syndrome (BS), an autosomal recessive disorder characterised by proportionate pre- and postnatal growth deficiency; sun-sensitive, telangiectatic, hypo- and hyperpigmented skin; predisposition to malignancy; and chromosomal instability [].
The HRDC (helicase and RNaseD C-terminal) domain is comprised of two orthogonally packed α-hairpin subdomains, and is involved in interactions with DNA and protein. It has been suggested that this domain plays a role dissolving double Holliday junctions efficiently [].HRDC domains are found at the C terminus of many RecQ helicases, including the human Bifunctional 3'-5' exonuclease/ATP-dependent helicase WRN and RecQ-like DNA helicase BLM [, ]. RecQ helicases have been shown to unwind DNA in an ATP-dependent manner. The structure of the HRDC domain consists of a 4-5 helical bundle of two orthogonally packed alpha-hairpins, and as such it resembles auxiliary domains in bacterial DNA helicases and other proteins that interact with nucleic acids. A positively charged region on the surface of the HRDC domain is able to interact with DNA.The HRDC domain is also present in eukaryotic and archaeal RNA polymerase II subunit RBP4, the N-terminal of which forms a heterodimerisation α-hairpin [, ].The HRDC domain has a putative role in nucleic acid binding. Mutations in the HRDC domain associated with the human BLM gene result in Bloom Syndrome (BS), an autosomal recessive disorder characterised by proportionate pre- and postnatal growth deficiency; sun-sensitive, telangiectatic, hypo- and hyperpigmented skin; predisposition to malignancy; and chromosomal instability [].
This superfamily represents the HRDC (helicase and RNaseD C-terminal) domain, which comprises two orthogonally packed α-hairpin subdomains, and is involved in interactions with DNA and protein. The HRDC (helicase and RNaseD C-terminal) domain is found at the C terminus of many RecQ helicases, including the human Bifunctional 3'-5' exonuclease/ATP-dependent helicase WRN and RecQ-like DNA helicase BLM (previously known as Werner and Bloom syndrome proteins) []. RecQ helicases have been shown to unwind DNA in an ATP-dependent manner. The structure of the HRDC domain consists of a 4-5 helical bundle of two orthogonally packed α-hairpins, and as such it resembles auxiliary domains in bacterial DNA helicases and other proteins that interact with nucleic acids. A positively charged region on the surface of the HRDC domain is able to interact with DNA.The HRDC domain is also present in eukaryotic and archaeal RNA polymerase II subunit RBP4, the N-terminal of which forms a heterodimerisation α-hairpin [, ].
This entry represents the DNA mismatch repair protein Msh2 (homologous to bacterial MutS) from eukaryotes. Msh2-Msh6 complex recognises base pair mismatches and small insertion/deletions in DNA and initiates repair []. Human Msh2-Msh6 complex has been shown to regulate BLM helicase in response tothe damaged DNA forks during double-stranded break repair []. Mismatch repair (MMR) is one of five major DNA repair pathways. The mismatch repair system recognises and repairs mispaired or unpaired nucleotides that result from errors in DNA replication. The most extensively studied general MMR system is the MutHLS pathway of the bacterium Escherichia coli. In the first step of the MutHLS pathway, the MutS protein (in the form of a dimer) binds to the site of a mismatch in double-stranded DNA. Through a complex interaction between MutS, MutL and MutH, a section of the newly replicated DNA strand (and thus the strand with the replication error) at the location of the mismatch bound by MutS is targeted for removal []. Homologues of MutS have been found in many species including eukaryotes, Archaea and other bacteria, and together these proteins have been grouped into the MutS family.
