Slx1—Slx4 is a second structure-specific endonuclease functionally redundant with Sgs1—Top3

Genes and Development - Tập 17 Số 14 - Trang 1768-1778 - 2003
William M. Fricke1, Steven J. Brill1
1Department of Molecular Biology and Biochemistry, Rutgers University, Piscataway, New Jersey, 08854, USA

Tóm tắt

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.

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Genes and Development

Tập 17 Số 14

1768-1778

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