Structural highlights
Function
[SEQA_ECOLI] Negative regulator of replication initiation, which contributes to regulation of DNA replication and ensures that replication initiation occurs exactly once per chromosome per cell cycle. Binds to pairs of hemimethylated GATC sequences in the oriC region, thus preventing assembly of replication proteins and re-initiation at newly replicated origins. Repression is relieved when the region becomes fully methylated. Can also bind to hemimethylated GATC sequences outside of oriC region. Binds, with less affinity, to fully methylated GATC sites and affects timing of replication. May play a role in chromosome organization and gene regulation.[1] [2] [3] [4] [5] [6]
Evolutionary Conservation
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Publication Abstract from PubMed
Escherichia coli SeqA binds clusters of transiently hemimethylated GATC sequences and sequesters the origin of replication, oriC, from methylation and premature reinitiation. Besides oriC, SeqA binds and organizes newly synthesized DNA at replication forks. Binding to multiple GATC sites is crucial for the formation of stable SeqA-DNA complexes. Here we report the crystal structure of the oligomerization domain of SeqA (SeqA-N). The structural unit of SeqA-N is a dimer, which oligomerizes to form a filament. Mutations that disrupt filament formation lead to asynchronous DNA replication, but the resulting SeqA dimer can still bind two GATC sites separated from 5 to 34 base pairs. Truncation of the linker between the oligomerization and DNA-binding domains restricts SeqA to bind two GATC sites separated by one or two full turns. We propose a model of a SeqA filament interacting with multiple GATC sites that accounts for both origin sequestration and chromosome organization.
Crystal structure of a SeqA-N filament: implications for DNA replication and chromosome organization.,Guarne A, Brendler T, Zhao Q, Ghirlando R, Austin S, Yang W EMBO J. 2005 Apr 20;24(8):1502-11. Epub 2005 Mar 31. PMID:15933720[7]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
References
- ↑ Lu M, Campbell JL, Boye E, Kleckner N. SeqA: a negative modulator of replication initiation in E. coli. Cell. 1994 May 6;77(3):413-26. PMID:8011018
- ↑ von Freiesleben U, Rasmussen KV, Schaechter M. SeqA limits DnaA activity in replication from oriC in Escherichia coli. Mol Microbiol. 1994 Nov;14(4):763-72. PMID:7891562
- ↑ Slater S, Wold S, Lu M, Boye E, Skarstad K, Kleckner N. E. coli SeqA protein binds oriC in two different methyl-modulated reactions appropriate to its roles in DNA replication initiation and origin sequestration. Cell. 1995 Sep 22;82(6):927-36. PMID:7553853
- ↑ Brendler T, Sawitzke J, Sergueev K, Austin S. A case for sliding SeqA tracts at anchored replication forks during Escherichia coli chromosome replication and segregation. EMBO J. 2000 Nov 15;19(22):6249-58. PMID:11080170 doi:10.1093/emboj/19.22.6249
- ↑ Skarstad K, Lueder G, Lurz R, Speck C, Messer W. The Escherichia coli SeqA protein binds specifically and co-operatively to two sites in hemimethylated and fully methylated oriC. Mol Microbiol. 2000 Jun;36(6):1319-26. PMID:10931282
- ↑ Sanchez-Romero MA, Busby SJ, Dyer NP, Ott S, Millard AD, Grainger DC. Dynamic distribution of seqa protein across the chromosome of escherichia coli K-12. MBio. 2010 May 18;1(1). pii: e00012-10. doi: 10.1128/mBio.00012-10. PMID:20689753 doi:10.1128/mBio.00012-10
- ↑ Guarne A, Brendler T, Zhao Q, Ghirlando R, Austin S, Yang W. Crystal structure of a SeqA-N filament: implications for DNA replication and chromosome organization. EMBO J. 2005 Apr 20;24(8):1502-11. Epub 2005 Mar 31. PMID:15933720
