Slx1—Slx4 is a second structure-specific endonuclease functionally redundant with Sgs1—Top3
Open Access
- 27 June 2003
- journal article
- Published by Cold Spring Harbor Laboratory in Journal of Bone and Joint Surgery
- Vol. 17 (14), 1768-1778
- https://doi.org/10.1101/gad.1105203
Abstract
The RecQ DNA helicases human BLM and yeast Sgs1 interact with DNA topoisomerase III and are thought to act on stalled replication forks to maintain genome stability. To gain insight into this mechanism, we previously identifiedSLX1andSLX4as genes that are required for viability and for completion of rDNA replication in the absence ofSGS1–TOP3. Here we show thatSLX1andSLX4encode a heteromeric structure-specific endonuclease. The Slx1–Slx4 nuclease is active on branched DNA substrates, particularly simple-Y, 5′-flap, or replication forkstructures. It cleaves the strand bearing the 5′ nonhomologous arm at the branch junction and generates ligatable nicked products from 5′-flap or replication fork substrates. Slx1 is the founding member of a family of proteins with a predicted URI nuclease domain and PHD-type zinc finger. This subunit displays weakstructure-specific endonuclease activity on its own, is stimulated 500-fold by Slx4, and requires the PHD finger for activity in vitro and in vivo. Both subunits are required in vivo for resistance to DNA damage by methylmethane sulfonate (MMS). We propose that Sgs1–Top3 acts at the termination of rDNA replication to decatenate stalled forks, and, in its absence, Slx1–Slx4 cleaves these stalled forks.Keywords
This publication has 52 references indexed in Scilit:
- The Mechanism of Mus81-Mms4 Cleavage Site Selection Distinguishes It from the Homologous Endonuclease Rad1-Rad10Molecular and Cellular Biology, 2003
- Mus81-Eme1 and Rqh1 Involvement in Processing Stalled and Collapsed Replication ForksOnline Journal of Public Health Informatics, 2002
- Mus81-Eme1 Are Essential Components of a Holliday Junction ResolvaseCell, 2001
- Evidence for BLM and Topoisomerase IIIalpha interaction in genomic stabilityHuman Molecular Genetics, 2001
- Mapping the DNA Topoisomerase III Binding Domain of the Sgs1 DNA HelicaseOnline Journal of Public Health Informatics, 2001
- RecQ Helicase and Topoisomerase III Comprise a Novel DNA Strand Passage Function: A Conserved Mechanism for Control of DNA RecombinationMolecular Cell, 1999
- Defending genome integrity during DNA replication: a proposed role for RecQ family helicasesBioEssays, 1999
- The Structure-selectivity and Sequence-preference of the Junction-resolving Enzyme CCE1 ofSaccharomyces cerevisiaeJournal of Molecular Biology, 1996
- Bloom's Syndrome: Evidence for an Increased Mutation Frequency in VivoScience, 1983
- Arrest of segregation leads to accumulation of highly intertwined catenated dimers: Dissection of the final stages of SV40 DNA replicationCell, 1981