ARS412 Summary Help

Systematic Name ARS412
Feature Type ARS
Description Putative replication origin; identified in multiple array studies, not yet confirmed by plasmid-based assay (1, 2, 3, 4 and see Summary Paragraph)
Chromosomal Location
ChrIV:316388 to 316971 | ORF Map | GBrowse
sequence information
ChrIV:316388 to 316971 | ORF Map | GBrowse
Last Update Coordinates: 2009-05-07 | Sequence: 2009-05-07
Retrieve sequences
Analyze Sequence
S288C only
S288C vs. other species
External Links All Associated Seq | OriDB | Search all NCBI (Entrez)
Primary SGDIDS000130172

Autonomously replicating sequences (ARSs) function as chromosomal replication origins in Saccharomyces cerevisiae, and play an essential role in chromosome maintenance (5, 6). During S phase, chromosomes are duplicated so that each mother cell retains, and each daughter cell receives, a full complement as a result of mitotic cell division. Each chromosome initiates replication at multiple sites at intervals of 40-100 kb, with each origin regulated to fire only once per cell cycle, mostly around mid-S phase, although different origins are activated continuously throughout S phase (7, 8, 9). Most origins are intergenic in nature, and only a subset operate during any given cell cycle, giving rise to highly-efficient origins that function in most cell cycles and extremely inefficient origins that are used in only a small percentage of cell cycles, as well as a range of efficiencies in between (8). Origins also fire in a characteristic order, which appears to be independent of the origin itself, but often correlates with the transcriptional activity of surrounding genes, with early-firing origins associated with active genes, and late-firing origins associated with silent genes (7).

ARSs have proven difficult to identify because they vary greatly in sequence and functional element composition, although they do share an elevated A-T content, interpreted to promote localized ease of DNA unwinding, which increases efficiency of replication initiation (10). ARSs are modular in structure, generally ~100-200 bp long, and depend on an exact match, or very near match, of an essential copy of an 11-base pair (bp) ARS consensus sequence (ACS), 5'-WTTTAYRTTTW-3', mutations in which abolish ARS function (11, 12). Some ARSs also contain additional near-match ACSs that are dispensable for function (11). Substantial sequence conservation has been observed in the 3 bp on either side of the essential match ACS, allowing for the identification of a 17-bp extended ACS (EACS), 5'-WWWWTTTAYRTTTWGTT-3' (11). The core ACS is part of "domain A", and is bound by the Origin Recognition Complex (ORC), a six-subunit DNA-dependent ATPase that functions as the replication initiator protein and launching pad for the assembly of the prereplication complex (pre-RC) (11). Immediately downstream of domain A (3' to the T-rich strand of the ACS) is "domain B", which exhibits little sequence conservation among ARSs and is composed of several nonredundant sequence elements (B1, B2, B3, B4), which vary from one ARS to another (11). Some, but not all, mutations in the B1 subelement can reduce the efficiency of ORC binding, suggesting that B1 functions with domain A as part of the ORC binding site (11). The B2 subelement, or DUE (DNA Unwinding Element), is AT-rich and serves as the site for the initial DNA unwinding, allowing the replication machinery to enter the DNA duplex in this area and assemble the first new nucleotides (13, 14). The B3 subelement is a 12-bp degenerate sequence that acts as a binding site for the transcriptional activator/repressor ARS binding factor 1 (ABF1) (11, 14). The function of the B4 subelement is as yet unknown (13). Some ARSs also have stimulatory sequences upstream of domain A (on the opposite side of the ACS) known as "domain C", as well as binding sites for the Rap1p transcription factor (13).

Last updated: 2006-05-09 Contact SGD

References cited on this page View Complete Literature Guide for ARS412
1) Wyrick JJ, et al.  (2001) Genome-wide distribution of ORC and MCM proteins in S. cerevisiae: high-resolution mapping of replication origins. Science 294(5550):2357-60
2) Feng W, et al.  (2006) Genomic mapping of single-stranded DNA in hydroxyurea-challenged yeasts identifies origins of replication. Nat Cell Biol 8(2):148-55
3) Raveendranathan M, et al.  (2006) Genome-wide replication profiles of S-phase checkpoint mutants reveal fragile sites in yeast. EMBO J 25(15):3627-39
4) Xu W, et al.  (2006) Genome-wide mapping of ORC and Mcm2p binding sites on tiling arrays and identification of essential ARS consensus sequences in S. cerevisiae. BMC Genomics 7():276
5) Deshpande AM and Newlon CS  (1992) The ARS consensus sequence is required for chromosomal origin function in Saccharomyces cerevisiae. Mol Cell Biol 12(10):4305-13
6) Yang C, et al.  (1999) Conservation of ARS elements and chromosomal DNA replication origins on chromosomes III of Saccharomyces cerevisiae and S. carlsbergensis. Genetics 152(3):933-41
7) Vujcic M, et al.  (1999) Activation of silent replication origins at autonomously replicating sequence elements near the HML locus in budding yeast. Mol Cell Biol 19(9):6098-109
8) Raghuraman MK, et al.  (2001) Replication dynamics of the yeast genome. Science 294(5540):115-21
9) Poloumienko A, et al.  (2001) Completion of replication map of Saccharomyces cerevisiae chromosome III. Mol Biol Cell 12(11):3317-27
10) Shirahige K, et al.  (1993) Location and characterization of autonomously replicating sequences from chromosome VI of Saccharomyces cerevisiae. Mol Cell Biol 13(8):5043-56
11) Theis JF and Newlon CS  (1997) The ARS309 chromosomal replicator of Saccharomyces cerevisiae depends on an exceptional ARS consensus sequence. Proc Natl Acad Sci U S A 94(20):10786-91
12) Newlon CS and Theis JF  (2002) DNA replication joins the revolution: whole-genome views of DNA replication in budding yeast. Bioessays 24(4):300-4
13) Theis JF, et al.  (1999) DNA sequence and functional analysis of homologous ARS elements of Saccharomyces cerevisiae and S. carlsbergensis. Genetics 152(3):943-52
14) Chang VK, et al.  (2003) Mcm1 binds replication origins. J Biol Chem 278(8):6093-100