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Genetics and Development

Infections and Immunity

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Structural Biology

Rita Cha group

Eukaryotic chromosome metabolism

Genome duplication and segregation are two fundamental processes in biology. We study the ways in which signal transduction regulates these events. A key component in eukaryotic chromosome metabolism is the ATR/ATM family of proteins. These evolutionarily conserved signal transduction proteins are involved in a number of chromosomal processes including DNA replication, recombination, and checkpoint regulation. Inactivation of these genes leads to cell death, genome instability, and meiotic dysfunction as well as the genetic disorders, Ataxia Telengiectasia (AT) and Seckle syndrome.

We use genetically tractable S. cerevisiae to study the molecular basis for the ATR/ATM functions. We found that inactivation of Mec1/Tel1, the budding yeast homologues of ATR/ATM, leads to chromosome breakage during proliferation and disruption of essential meiotic chromosomal processes. Currently, our research focuses on the roles of Mec1/Tel1 in meiotic recombination and fragile site stability. The results of our studies will provide insights into how disruption of these genes leads to failure of fundamental chromosomal processes.

Research projects

Selected publications

Carballo, JA; Johnson, AL; Sedgwick, SG and Cha, RS (2008)
Phosphorylation of the axial element protein Hop1 by Mec1/Tel1 ensures meiotic interhomolog recombination.
Cell 132, 758-70 PubMed abstract
Carballo, JA and Cha, RS (2007)
Meiotic roles of Mec1, a budding yeast homolog of mammalian ATR/ATM.
Chromosome Research 15, 539-50 PubMed abstract
Machín F, Torres-Rosell J, De Piccoli G, Carballo JA, Cha RS, Jarmuz A, Aragón L. (2006)
Transcription of ribosomal genes can cause nondisjunction.
Journal of Cell Biology 173, 893-903 PubMed abstract
Cha, R.S., and Kleckner, N. (2002)
ATR Homolog Mec1 Promotes Fork Progression, Thus Averting Breaks in Replication Slow Zones.
Science 297, 602-6 PubMed abstract