D
IPR002121

HRDC domain

InterPro entry
Short nameHRDC_dom
Overlapping
homologous
superfamilies
 
domain relationships

Description

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
[5]
.

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
[5, 1]
. 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
[3, 4]
.

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
[2]
.

References

1.The three-dimensional structure of the HRDC domain and implications for the Werner and Bloom syndrome proteins. Liu Z, Macias MJ, Bottomley MJ, Stier G, Linge JP, Nilges M, Bork P, Sattler M. Structure 7, 1557-66, (1999). View articlePMID: 10647186

2.A putative nucleic acid-binding domain in Bloom's and Werner's syndrome helicases. Morozov V, Mushegian AR, Koonin EV, Bork P. Trends Biochem. Sci. 22, 417-8, (1997). View articlePMID: 9397680

3.Structures of complete RNA polymerase II and its subcomplex, Rpb4/7. Armache KJ, Mitterweger S, Meinhart A, Cramer P. J. Biol. Chem. 280, 7131-4, (2005). View articlePMID: 15591044

4.Structure of an archaeal homolog of the eukaryotic RNA polymerase II RPB4/RPB7 complex. Todone F, Brick P, Werner F, Weinzierl RO, Onesti S. Mol. Cell 8, 1137-43, (2001). View articlePMID: 11741548

5.Crystal structure of the Bloom's syndrome helicase indicates a role for the HRDC domain in conformational changes. Newman JA, Savitsky P, Allerston CK, Bizard AH, Ozer O, Sarlos K, Liu Y, Pardon E, Steyaert J, Hickson ID, Gileadi O. Nucleic Acids Res 43, 5221-35, (2015). PMID: 25901030

GO terms

biological process

  • None

cellular component

  • None

Cross References

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