Human RECQL5β stimulates flap endonuclease 1
Authors:
Open Access
- 16 January 2010
- journal article
- Published by Oxford University Press (OUP) in Nucleic Acids Research
- Vol. 38 (9) , 2904-2916
Abstract
Human RECQL5 is a member of the RecQ helicase family which is implicated in genome maintenance. Five human members of the family have been identified; three of them, BLM, WRN and RECQL4 are associated with elevated cancer risk. RECQL1 and RECQL5 have not been linked to any human disorder yet; cells devoid of RECQL1 and RECQL5 display increased chromosomal instability. Here, we report the physical and functional interaction of the large isomer of RECQL5, RECQL5β, with the human flap endonuclease 1, FEN1, which plays a critical role in DNA replication, recombination and repair. RECQL5β dramatically stimulates the rate of FEN1 cleavage of flap DNA substrates. Moreover, we show that RECQL5β and FEN1 interact physically and co-localize in the nucleus in response to DNA damage. Our findings, together with the previous literature on WRN, BLM and RECQL4's stimulation of FEN1, suggests that the ability of RecQ helicases to stimulate FEN1 may be a general feature of this class of enzymes. This could indicate a common role for the RecQ helicases in the processing of oxidative DNA damage.Keywords
This publication has 59 references indexed in Scilit:
- Direct Inhibition of RNA Polymerase II Transcription by RECQL5Journal of Biological Chemistry, 2009
- Direct and indirect roles of RECQL4 in modulating base excision repair capacityHuman Molecular Genetics, 2009
- Recql5 Plays an Important Role in DNA Replication and Cell Survival after Camptothecin TreatmentMolecular Biology of the Cell, 2009
- A RECQ5–RNA polymerase II association identified by targeted proteomic analysis of human chromatinProceedings of the National Academy of Sciences, 2008
- Flap Endonuclease 1 Contributes to Telomere StabilityCurrent Biology, 2008
- Comprehensive Mapping of the C-Terminus of Flap Endonuclease-1 Reveals Distinct Interaction Sites for Five Proteins That Represent Different DNA Replication and Repair PathwaysJournal of Molecular Biology, 2008
- RECQL5/Recql5 helicase regulates homologous recombination and suppresses tumor formation via disruption of Rad51 presynaptic filamentsGenes & Development, 2007
- RECQL, a Member of the RecQ Family of DNA Helicases, Suppresses Chromosomal InstabilityMolecular and Cellular Biology, 2007
- Human RECQ5β helicase promotes strand exchange on synthetic DNA structures resembling a stalled replication forkNucleic Acids Research, 2006
- Flap endonuclease 1: a novel tumour suppresser proteinTrends in Biochemical Sciences, 2003