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Gene Review

CHL1  -  Chl1p

Saccharomyces cerevisiae S288c

Synonyms: ATP-dependent RNA helicase CHL1, CTF1, Chromosome loss protein 1, Chromosome transmission fidelity protein 1, LPA9, ...
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Disease relevance of CHL1


High impact information on CHL1


Biological context of CHL1

  • Within the budding yeast genome, Chl1p exhibits the highest degree of sequence similarity to human CHL1 isoforms and BACH1 [4].
  • Using a functional as well as a cytological assay, we demonstrate that CTF8, CHL1 and CTF4 are essential for cohesion between sister centromeres during meiosis but dispensable for cohesin's association with centromeric DNA [5].
  • The deduced amino acid sequence predicts a hydrophobic peptide consisting of 601 amino acids, having a molecular mass of 68.1 kDa, composed in part of 12 hydrophobic segments, and sharing significant similarities with a nitrate transport protein encoded by the CHL1 gene of Arabidopsis thaliana [6].
  • The yeast CHL1 helicase has been linked to maintenance of the high fidelity of chromosome transmission during mitosis [7].
  • CHL1 encodes a 99 kDa predicted protein with an ATP binding site consensus, a putative helix-turn-helix DNA binding motif, and homology to helicases [8].

Anatomical context of CHL1

  • The human homologue of the yeast CHL1 gene is a novel keratinocyte growth factor-regulated gene [9].
  • Furthermore, expression of the CHL1-related mRNAs is lost when human K562 cells cease to proliferate and terminally differentiate in response to phorbol ester treatments [7].
  • Here we show that these two distinct human CHL1-related mRNAs and proteins (hCHLR1 and hCHLR2) are expressed only in proliferating human cell lines [7].
  • Furthermore, contrasting the dual-affinity nitrate transport activity of CHL1, OsNRT1 displayed only low-affinity nitrate transport activity in Xenopus oocytes, with a K(m) value of approximately 9 mM [10].

Associations of CHL1 with chemical compounds

  • CTF7, which lacks the entire proline-rich region previously thought to mediate transcriptional activation by CTF proteins, enhances transcription to a greater degree than full-length CTF1, which contains the putative activation domain [11].
  • When chl1 cells were treated with relatively low levels of MMS in S-phase, they lost viability [12].

Other interactions of CHL1

  • Consistent with genetic interactions, Chl1p physically associates with Ctf7p/Eco1p both in vivo and in vitro [4].
  • Our findings document a novel role for Chl1p in sister-chromatid cohesion and provide new insights into the possible mechanisms through which DNA helicases may contribute to cancer progression when mutated [4].
  • Chl1p also acts synergistically with Sir2p to suppress rDNA recombination [13].

Analytical, diagnostic and therapeutic context of CHL1

  • Molecular cloning and sequencing of the full-length cDNA revealed a strong homology with the yeast CHL1 gene [9].
  • Homothallic strains of yeast containing a null allele of CHL1 exhibited almost random selection of the donor locus in a MATa background but were normal in their ability to select HMR in a MAT alpha background [14].
  • Using site-directed mutagenesis, I show that mutations that are predicted to abolish ATP binding in CHL1 inactivate its function in chromosome segregation [8].
  • Our results indicate that Chl1p participates in the process of donor selection and are consistent with a model in which Chl1p helps establish an intrinsic bias in donor preference [14].
  • In order to identify residues crucial for its activator function, a pool of CTF1 mutants was cloned and fused to the bacterial repressor LexA [15].


  1. Stimulation of DNA replication in Saccharomyces cerevisiae by a glutamine- and proline-rich transcriptional activation domain. Li, R. J. Biol. Chem. (1999) [Pubmed]
  2. A proline-rich TGF-beta-responsive transcriptional activator interacts with histone H3. Alevizopoulos, A., Dusserre, Y., Tsai-Pflugfelder, M., von der Weid, T., Wahli, W., Mermod, N. Genes Dev. (1995) [Pubmed]
  3. The CHL 1 (CTF 1) gene product of Saccharomyces cerevisiae is important for chromosome transmission and normal cell cycle progression in G2/M. Gerring, S.L., Spencer, F., Hieter, P. EMBO J. (1990) [Pubmed]
  4. Chl1p, a DNA helicase-like protein in budding yeast, functions in sister-chromatid cohesion. Skibbens, R.V. Genetics (2004) [Pubmed]
  5. Sister-chromatid cohesion mediated by the alternative RF-CCtf18/Dcc1/Ctf8, the helicase Chl1 and the polymerase-alpha-associated protein Ctf4 is essential for chromatid disjunction during meiosis II. Petronczki, M., Chwalla, B., Siomos, M.F., Yokobayashi, S., Helmhart, W., Deutschbauer, A.M., Davis, R.W., Watanabe, Y., Nasmyth, K. J. Cell. Sci. (2004) [Pubmed]
  6. Isolation and characterization of a Saccharomyces cerevisiae peptide transport gene. Perry, J.R., Basrai, M.A., Steiner, H.Y., Naider, F., Becker, J.M. Mol. Cell. Biol. (1994) [Pubmed]
  7. Characterization of putative human homologues of the yeast chromosome transmission fidelity gene, CHL1. Amann, J., Kidd, V.J., Lahti, J.M. J. Biol. Chem. (1997) [Pubmed]
  8. CHL1 is a nuclear protein with an essential ATP binding site that exhibits a size-dependent effect on chromosome segregation. L Holloway, S. Nucleic Acids Res. (2000) [Pubmed]
  9. The human homologue of the yeast CHL1 gene is a novel keratinocyte growth factor-regulated gene. Frank, S., Werner, S. J. Biol. Chem. (1996) [Pubmed]
  10. Cloning and functional characterization of a constitutively expressed nitrate transporter gene, OsNRT1, from rice. Lin, C.M., Koh, S., Stacey, G., Yu, S.M., Lin, T.Y., Tsay, Y.F. Plant Physiol. (2000) [Pubmed]
  11. Transcriptional activation by CTF proteins is mediated by a bipartite low-proline domain. Altmann, H., Wendler, W., Winnacker, E.L. Proc. Natl. Acad. Sci. U.S.A. (1994) [Pubmed]
  12. The budding yeast protein Chl1p is required to preserve genome integrity upon DNA damage in S-phase. Laha, S., Das, S.P., Hajra, S., Sau, S., Sinha, P. Nucleic Acids Res. (2006) [Pubmed]
  13. The budding yeast protein Chl1p has a role in transcriptional silencing, rDNA recombination, and aging. Das, S.P., Sinha, P. Biochem. Biophys. Res. Commun. (2005) [Pubmed]
  14. Mutations affecting donor preference during mating type interconversion in Saccharomyces cerevisiae. Weiler, K.S., Szeto, L., Broach, J.R. Genetics (1995) [Pubmed]
  15. Transcriptional activation of NFI/CTF1 depends on a sequence motif strongly related to the carboxyterminal domain of RNA polymerase II. Wendler, W., Altmann, H., Ludwig-Winnacker, E. Nucleic Acids Res. (1994) [Pubmed]
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