Structure of an XPF endonuclease with and without DNA suggests a model for substrate recognition

@article{Newman2005StructureOA,
  title={Structure of an XPF endonuclease with and without DNA suggests a model for substrate recognition},
  author={Matthew Newman and Judith Murray-Rust and John Martin Lally and Jana Rudolf and Andrew J. Fadden and Philip P. Knowles and Malcolm F. White and Neil Q. McDonald},
  journal={The EMBO Journal},
  year={2005},
  volume={24},
  url={https://api.semanticscholar.org/CorpusID:6154555}
}
A model in which XPF distorts the 3′ flap substrate in order to engage both binding sites and promote strand cleavage is proposed, which rationalises published biochemical data and implies a novel role for the ERCC1 subunit of eukaryotic XPF complexes.
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PCNA and XPF cooperate to distort DNA substrates

This work investigates the solution structure of the 3′-flap substrate bound to XPF in the presence and absence of PCNA using intramolecular Förster resonance energy transfer (FRET), and demonstrates that recognition of the flap substrate by XPF involves major conformational changes of the DNA.

DNA end-directed and processive nuclease activities of the archaeal XPF enzyme

The importance of the downstream duplex in directing the endonuclease activity of crenarchaeal XPF, which is similar to that of Mus81-Eme1, is demonstrated and a mechanistic basis for this control is suggested.

Structure and function of a novel endonuclease acting on branched DNA substrates

Biochemical and structural studies indicate that NucS orthologues use a non‐catalytic ssDNA‐binding domain to regulate the cleavage activity at another site, thus resulting into the specific cleavage at double‐stranded DNA (dsDNA)/ssDNA junctions on branched DNA substrates.

Analysis of the XPA and ssDNA-binding surfaces on the central domain of human ERCC1 reveals evidence for subfunctionalization

It is discussed the possibility that after XPF gene duplication, the redundant ERCC1 central domain acquired novel functions, thereby increasing the fidelity of eukaryotic DNA repair.

The structure of the XPF-ssDNA complex underscores the distinct roles of the XPF and ERCC1 helix- hairpin-helix domains in ss/ds DNA recognition.

Structure of the C‐terminal half of UvrC reveals an RNase H endonuclease domain with an Argonaute‐like catalytic triad

The crystal structure of the C‐terminal half of UvrC is described, which contains the catalytic domain responsible for 5′ incision and a helix–hairpin–helix–domain that is implicated in DNA binding.

Structural and functional analyses of an archaeal XPF/Rad1/Mus81 nuclease: asymmetric DNA binding and cleavage mechanisms.

Fluorescence-based incision assay for human XPF–ERCC1 activity identifies important elements of DNA junction recognition

The minimal substrate requirements for cleavage of stem–loop substrates are defined allowing us to develop a real-time fluorescence-based assay to measure endonuclease activity and it is shown that changes in the sequence of the duplex upstream of the incision site results in up to 100-fold variation in cleavage rate by XPF-ERCC1.

Crystal structure and DNA binding functions of ERCC1, a subunit of the DNA structure-specific endonuclease XPF-ERCC1.

It is shown that a truncated form of XPF lacking the N-terminal helicase-like domain in complex with ERCC1 exhibits a structure-specific endonuclease activity with similar specificity to that of full-length XPF-ERCC1.

The HhH domain of the human DNA repair protein XPF forms stable homodimers

The higher stability of the XPF HhH complexes under various experimental conditions, determined using CD and NMR spectroscopy and mass spectrometry, is well explained by the structural differences that exist between the Hhh domains of the two complexes.
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50 References

Novel endonuclease in Archaea cleaving DNA with various branched structure.

This protein, designated as Hef (helicase-associated endonuclease for fork-structured DNA), may be a prototypical enzyme for resolving stalled forks during DNA replication, as well as working at nucleotide excision repair.

The active site of the DNA repair endonuclease XPF–ERCC1 forms a highly conserved nuclease motif

Alignment of the active site region of XPF with proteins belonging to the Mus81 family and a putative archaeal RNA helicase family reveals that seven of the residues ofXPF involved in nuclease activity are absolutely conserved in the three protein families, indicating that they share a common nucleasing motif.

DNA Structural Elements Required for ERCC1-XPF Endonuclease Activity*

Recombinant ERCC1-XPF, purified from insect cells, was found to cleave stem-loop substrates at the DNA junction in the absence of other proteins like replication protein A, showing that the structure-specific endonuclease activity is intrinsic to the complex.

Structural basis for recruitment of translesion DNA polymerase Pol IV/DinB to the β‐clamp

A first structure of an entire domain of a binding partner with an assembled clamp reveals a substantial secondary interface, which maintains the polymerase in an inactive orientation, and may regulate the switch between replicative and Y‐family DNA polymerases in response to a template strand lesion

Structural Basis for FEN-1 Substrate Specificity and PCNA-Mediated Activation in DNA Replication and Repair

An archaeal XPF repair endonuclease dependent on a heterotrimeric PCNA

The PCNA‐XPF complex acts as a structure‐specific nuclease on a similar range of DNA flap, bubble and junction substrates as the human protein, suggesting a fundamental conservation through billions of years of evolution.

Structural basis for recruitment of human flap endonuclease 1 to PCNA

The structure involving the full‐length enzyme has revealed additional interfaces that are involved in the core domain that maintain the enzyme in an inactive 'locked‐down' orientation and might be utilized in rapid DNA‐tracking by preserving the central hole of PCNA for sliding along the DNA.

Activity of individual ERCC1 and XPF subunits in DNA nucleotide excision repair.

Protein sequence comparison revealed similarity between the ERCC1 family and the C-terminal region of the XPF family, including the regions of both proteins that are necessary for the ER CC1-XPF heterodimeric interaction, which suggests that the ERcc1 and XPF families are related via an ancient duplication.

X-ray and biochemical anatomy of an archaeal XPF/Rad1/Mus81 family nuclease: similarity between its endonuclease domain and restriction enzymes.

Solution structure and DNA‐binding properties of the C‐terminal domain of UvrC from E.coli

The C‐terminal domain of the UvrC protein (UvrC CTD) is essential for 5′ incision in the prokaryotic nucleotide excision repair process and is shown to mediate structure‐specific DNA binding.