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The role of dna replication factors in the establishment of cohesion between sister chromatids

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Ms Armelle LENGRONNE is a graduate student in my laboratory in Montpellier, France. She got her higher education from University Pierre & Marie Curie in Paris, then did her Diploma work with Dr. C. Jackson at the CEA in Saclay, on intracellular trafficking in yeast. She was one of the best rated student there, and as such, obtained a competitive PhD fellowship from the French government. I was delighted when she decided, in the fall of 1998, to join my laboratory for her thesis work. I know Armelle quite well as I interact with her on a daily basis. She is a very talented person, determined, well-read and critical of her own results, which are all attributes of a promising young scientist. Within short time. Armelle developed a series of techniques to monitor DNA replication globally and locally using BrdU incorporation in yeast cells (Lengronne et al. 2001. Nucl. Ac. Res. 29:1433). This paper is important as it contains the groundwork that paves the way for understanding the dynamics of chromosomes duplication. Armelle then used these techniques along with others to show that yeast cells lacking the cyclic-dependent kinase (CDK) inhibitor Sic1 initiate DNA replication from a reduced number of origins and, as a consequence, progress more slowly through S phase. Like its mammalian counterparts p21 and p27, the CDK inhibitor Sic1 is important for maintaining genomic integrity. Armelle discovered that sic1Delta mutants fail to partition sister chromatids properly, probably as a consequence of perturbed replication, and frequently lose or rearrange instability in mitosis by altering the number and/or positioning of replication origins. This work is now submitted, Armelle being first author. Another publication which describes the consequences for mitosis of altering the dynamics of DNA replication is in preparation. I personally rank Armelle within the top 10% of students I have met or supervised in several countries. She is highly motivated for science, extremely hard-working and the current workhorse of my laboratory. Armelle is technically very good, masters a variety of techniques (in yeast genetics, biochemistry and cell biology), and can handle several experiments or projects in parallel. She is afloat with the literature and comes up with good ideas. Armelle is friendly but speaks openly when needed. She likes to collaborate with other lab members and is a excellent teacher for new students. She works independently and is now ready to mature further by a rich post-doctoral experience, with exposure to international science in a competitive environment. She is keen about doing a post-doc, even two if necessary. My impression is that she has the stamina and talent to succeed in science. For her post-doc, she has chosen a research project that perfectly bridges the topic from my lab (DNA replication) with that of the host lab (mitosis). Therefore she will be able to make the best use of her knowledge while also acquiring new competences. Armelle will turn out, I have no doubt, as a real asset for the lab she is joining. For all those reasons, I give my full support to Armelle's application for a Post-Doctoral Fellowship.

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