This entry represents the domain that is responsible for the 3'-5' exonuclease proofreading activity of Escherichia coli DNA polymerase I (polI) and other enzymes which catalyse the hydrolysis of unpaired or mismatched nucleotides. This domain consists of the amino-terminal half of the Klenow fragment in E. coli polI and is also found in the Bifunctional 3'-5' exonuclease/ATP-dependent helicase WRN (also known as Werner syndrome helicase), focus forming activity 1 protein (FFA-1) and ribonuclease D (RNase D) [].Werner syndrome is a human genetic disorder causing premature ageing; the WRN protein has helicase activity in the 3'-5' direction [, ]. The FFA-1 protein is required for formation of a replication foci and also has helicase activity; it is a homologue of the WRN protein []. RNase D is a 3'-5' exonuclease involved in tRNA processing. Also found in this family is the autoantigen PM/Scl thought to be involved in polymyositis-scleroderma overlap syndrome.This domain is also found in some DNA polymerases from phages, including the DNA polymerase from Escherichia phage T5, exonucleolytic activity [], and the DNA polymerase DpoZ from Acinetobacter phage SH-Ab 15497, which preferentially incorporates the non-canonical base aminoadenine/dZTP instead of adenine into the synthesized DNA [].
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 [, ].
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 [].
