Research Interests

Zakian's major contributions are in telomere biology and replication fork progression. Her lab isolated the first single-strand DNA binding proteins, prototypes of Pot1, which protect telomeres from degradation. They discovered telomere position effect, the epigenetic silencing of genes near yeast telomeres. They found a new step in telomere biology, strand-specific degradation of telomeric DNA, which generates extended G-rich single-stranded tails. They discovered that the Pif1 DNA helicase inhibits telomere lengthening and de novo telomere addition by ejecting telomerase from DNA ends. They described two pathways that recruit telomerase to yeast telomeres, one acting in G1 and the other in late S/G2 phase. They found that components of two multi-protein complexes regulate the abundance and activity of telomerase subunits: Cdc48 complex (Est1) and RNaseP/MRP proteins (telomerase RNA). They documented the importance of Pif1 family helicases in promoting replication fork movement past naturally occurring obstacles, such as non-nucleosomal protein complexes, RNA-DNA hybrids (R-loops) and G-quadruplex DNA. They found that the most highly RNA Polymerase II transcribed genes are potent inhibitors of fork progression and that expanded tracts of tri-nucleotide repeats cause fork slowing and DNA breakage in yeast. Zakian is also known for her advocacy of women and under-represented minorities in science.

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Section 26: Genetics