Conferring substrate specificity to DNA helicases: role of the RecQ HRDC domain - PubMed (original) (raw)

. 2005 Aug;13(8):1173-82.

doi: 10.1016/j.str.2005.04.018.

Affiliations

• PMID: 16084389
• DOI: 10.1016/j.str.2005.04.018

Free article

Conferring substrate specificity to DNA helicases: role of the RecQ HRDC domain

Douglas A Bernstein et al. Structure. 2005 Aug.

Free article

Abstract

RecQ DNA helicases are multidomain enzymes that play pivotal roles in genome maintenance pathways. While the ATPase and helicase activities of these enzymes can be attributed to the conserved catalytic core domain, the role of the Helicase-and-RNase-D-C-terminal (HRDC) domain in RecQ function has yet to be elucidated. Here, we report the crystal structure of the E. coli RecQ HRDC domain, revealing a globular fold that resembles known DNA binding domains. We show that this domain preferentially binds single-stranded DNA and identify its DNA binding surface. HRDC domain mutations in full-length RecQ lead to surprising differences in its structure-specific DNA binding properties. These data support a model in which naturally occurring variations in DNA binding residues among diverse RecQ homologs serve to target these enzymes to distinct substrates and provide insight into a mechanism whereby RecQ enzymes have evolved distinct functions in organisms that encode multiple recQ genes.

PubMed Disclaimer

Similar articles

• The HRDC domain oppositely modulates the unwinding activity of E. coli RecQ helicase on duplex DNA and G-quadruplex.
  Teng FY, Wang TT, Guo HL, Xin BG, Sun B, Dou SX, Xi XG, Hou XM. Teng FY, et al. J Biol Chem. 2020 Dec 18;295(51):17646-17658. doi: 10.1074/jbc.RA120.015492. J Biol Chem. 2020. PMID: 33454004 Free PMC article.
• Three tandem HRDC domains have synergistic effect on the RecQ functions in Deinococcus radiodurans.
  Huang L, Hua X, Lu H, Gao G, Tian B, Shen B, Hua Y. Huang L, et al. DNA Repair (Amst). 2007 Feb 4;6(2):167-76. doi: 10.1016/j.dnarep.2006.09.006. Epub 2006 Nov 7. DNA Repair (Amst). 2007. PMID: 17085080
• The HRDC domain of E. coli RecQ helicase controls single-stranded DNA translocation and double-stranded DNA unwinding rates without affecting mechanoenzymatic coupling.
  Harami GM, Nagy NT, Martina M, Neuman KC, Kovács M. Harami GM, et al. Sci Rep. 2015 Jun 11;5:11091. doi: 10.1038/srep11091. Sci Rep. 2015. PMID: 26067769 Free PMC article.
• Probing the structural basis of RecQ helicase function.
  Vindigni A, Marino F, Gileadi O. Vindigni A, et al. Biophys Chem. 2010 Jul;149(3):67-77. doi: 10.1016/j.bpc.2010.03.012. Epub 2010 Mar 20. Biophys Chem. 2010. PMID: 20392558 Review.
• RecQ helicases and topoisomerases: implications for genome stability in humans.
  Franchitto A. Franchitto A. Ital J Biochem. 2007 Jun;56(2):115-21. Ital J Biochem. 2007. PMID: 17722652 Review.

Cited by

• Recognition and unfolding of human telomeric G-quadruplex by short peptide binding identified from the HRDC domain of BLM helicase.
  Sharma T, Kundu N, Kaur S, Chakraborty A, Mahto AK, Dewangan RP, Shankaraswamy J, Saxena S. Sharma T, et al. RSC Adv. 2022 Aug 8;12(34):21760-21769. doi: 10.1039/d2ra03646k. eCollection 2022 Aug 4. RSC Adv. 2022. PMID: 36043100 Free PMC article.
• The toposiomerase IIIalpha-RMI1-RMI2 complex orients human Bloom's syndrome helicase for efficient disruption of D-loops.
  Harami GM, Pálinkás J, Seol Y, Kovács ZJ, Gyimesi M, Harami-Papp H, Neuman KC, Kovács M. Harami GM, et al. Nat Commun. 2022 Feb 3;13(1):654. doi: 10.1038/s41467-022-28208-9. Nat Commun. 2022. PMID: 35115525 Free PMC article.
• The HRDC domain oppositely modulates the unwinding activity of E. coli RecQ helicase on duplex DNA and G-quadruplex.
  Teng FY, Wang TT, Guo HL, Xin BG, Sun B, Dou SX, Xi XG, Hou XM. Teng FY, et al. J Biol Chem. 2020 Dec 18;295(51):17646-17658. doi: 10.1074/jbc.RA120.015492. J Biol Chem. 2020. PMID: 33454004 Free PMC article.
• Structural basis for guide RNA trimming by RNase D ribonuclease in Trypanosoma brucei.
  Gao Y, Liu H, Zhang C, Su S, Chen Y, Chen X, Li Y, Shao Z, Zhang Y, Shao Q, Li J, Huang Z, Ma J, Gan J. Gao Y, et al. Nucleic Acids Res. 2021 Jan 11;49(1):568-583. doi: 10.1093/nar/gkaa1197. Nucleic Acids Res. 2021. PMID: 33332555 Free PMC article.
• Structure of the helicase core of Werner helicase, a key target in microsatellite instability cancers.
  Newman JA, Gavard AE, Lieb S, Ravichandran MC, Hauer K, Werni P, Geist L, Böttcher J, Engen JR, Rumpel K, Samwer M, Petronczki M, Gileadi O. Newman JA, et al. Life Sci Alliance. 2020 Nov 16;4(1):e202000795. doi: 10.26508/lsa.202000795. Print 2021 Jan. Life Sci Alliance. 2020. PMID: 33199508 Free PMC article.

Publication types

MeSH terms

Substances

LinkOut - more resources

• Full Text Sources

  • Elsevier Science

• Molecular Biology Databases

  • BioCyc