M. E. O'Donnell

Adaptive capacity of a DNA polymerase clamp-loader ATPase complex

The paper shows that single point mutations can restore function to a defective DNA polymerase clamp-loader complex by compensating for reduced affinity between the clamp loader and the sliding clamp.

Molecular choreography of primer synthesis by the eukaryotic Pol α-primase

This study uses cryo-EM to analyze the structural dynamics of yeast Pol α-primase during primer synthesis, revealing how RNA primers are transferred to DNA polymerase and how primer length is regulated.

Structures of 9-1-1 DNA checkpoint clamp loading at gaps from start to finish and ramification to biology

This paper reports high-resolution structures of Rad24-RFC loading 9-1-1 onto DNA gaps, showing preference for ssDNA gaps and revealing a unique mechanism for clamp loading and DNA repair.

Cryo-EM structures reveal that RFC recognizes both the 3'- and 5'-DNA ends to load PCNA onto gaps for DNA repair

Rad24-RFC loads the 9-1-1 clamp by inserting DNA from the top of a wide-open ring, opposite the mechanism of RFC/PCNA

This paper reveals the mechanism by which Rad24-RFC loads the 9-1-1 clamp onto DNA by inserting ssDNA from the top of an open ring, differing from RFC/PCNA loading.

Nucleosome-directed replication origin licensing independent of a consensus DNA sequence

This study shows that the yeast origin recognition complex can bind nucleosomes and license replication origins without requiring a consensus DNA sequence, suggesting this mechanism is conserved across eukaryotes.

Allosteric communication in DNA polymerase clamp loaders relies on a critical hydrogen-bonded junction

The paper identifies a hydrogen-bonded junction in DNA polymerase clamp loaders that is critical for allosteric communication, preserved across diverse AAA+ ATPases.

Supporting evidence for DNA shearing as a mechanism for origin unwinding in eukaryotes

The paper provides evidence that CMG complexes unwind DNA by shearing it apart while binding only one strand, using an origin mimic DNA with specific structural features.

Ctf4 organizes sister replisomes and Pol alpha into a replication factory

The paper shows Ctf4 organizes sister replisomes and Pol alpha into a replication factory by dimerizing CMG helicase and binding one Pol-primase.

Tunability of DNA polymerase stability during eukaryotic DNA replication

The paper shows how DNA polymerase stability and exchange dynamics in the yeast replisome are tuned by local concentrations, enabling efficient replication and adaptation to genomic challenges.

Replisome preservation by a single-stranded DNA gate in the CMG helicase

The paper shows CMG helicase opens a single-stranded DNA gate to traverse forked junctions and resume replication after DNA damage, with Mcm10 facilitating this process.

Mcm10 functions to isomerize CMG-DNA for replisome bypass of DNA blocks

This study shows Mcm10 enables CMG helicase to bypass DNA blocks on the non-tracking strand by isomerizing the CMG-DNA complex.