Publications

BibTex format

@article{Hu:2020:10.1038/s41467-020-18964-x,
author = {Hu, Y and Tareen, A and Sheu, Y-J and Ireland, WT and Speck, C and Li, H and Joshua-Tor, L and Kinney, JB and Stillman, B},
doi = {10.1038/s41467-020-18964-x},
journal = {Nature Communications},
title = {Evolution of DNA replication origin specification and gene silencing mechanisms},
url = {http://dx.doi.org/10.1038/s41467-020-18964-x},
volume = {11},
year = {2020}
}

Download

RIS format (EndNote, RefMan)

TY  - JOUR
AB  - DNA replication in eukaryotic cells initiates from replication origins that bind the Origin Recognition Complex (ORC). Origin establishment requires well-defined DNA sequence motifs in Saccharomyces cerevisiae and some other budding yeasts, but most eukaryotes lack sequence-specific origins. A 3.9 Å structure of S. cerevisiae ORC-Cdc6-Cdt1-Mcm2-7 (OCCM) bound to origin DNA revealed that a loop within Orc2 inserts into a DNA minor groove and an α-helix within Orc4 inserts into a DNA major groove. Using a massively parallel origin selection assay coupled with a custom mutual-information-based modeling approach, and a separate analysis of whole-genome replication profiling, here we show that the Orc4 α-helix contributes to the DNA sequence-specificity of origins in S. cerevisiae and Orc4 α-helix mutations change genome-wide origin firing patterns. The DNA sequence specificity of replication origins, mediated by the Orc4 α-helix, has co-evolved with the gain of ORC-Sir4-mediated gene silencing and the loss of RNA interference.
AU  - Hu,Y
AU  - Tareen,A
AU  - Sheu,Y-J
AU  - Ireland,WT
AU  - Speck,C
AU  - Li,H
AU  - Joshua-Tor,L
AU  - Kinney,JB
AU  - Stillman,B
DO  - 10.1038/s41467-020-18964-x
PY  - 2020///
SN  - 2041-1723
TI  - Evolution of DNA replication origin specification and gene silencing mechanisms
T2  - Nature Communications
UR  - http://dx.doi.org/10.1038/s41467-020-18964-x
UR  - http://hdl.handle.net/10044/1/83874
VL  - 11
ER  -

Download

ProfessorChristianSpeck

Contact

Location

Summary

Citation

BibTex format

RIS format (EndNote, RefMan)