Anna Malkova (University of Iowa)

Anna Malkova (University of Iowa)

Butler Seminar Series

Event Date/Location

November 21, 2016 - 12:00 pm
Thomas Laboratory 003

Speaker

  • Picture of Dr. Malkova

    Anna Malkova

    Professor
    University of Iowa

    Anna Malkova received her BS in Biology and Ph.D. in Genetics from St. Petersburg State University (Russia). She performed her postdoctoral training in Molecular Genetics at Brandeis University in the laboratory of Dr. James Haber where she became interested in the mechanisms of DNA repair. She was recruited as an Assistant Professor by the Indiana University Purdue University Indianapolis in 2003, where she worked at the department of Biology for 10 years. She became an Associate Professor at the department of Biology of the University of Iowa and a member of the University of Iowa Genetic Cluster in 2014. The research conducted in Malkova’s laboratory is using baking yeast as a model, and is aimed to unravel mechanisms responsible for repair of double-strand DNA breaks (DSBs), which are dangerous because their imprecise or faulty repair often leads to mutations and chromosome aberrations that cause genetic diseases and cancer. An important focus of research in the lab is one pathway of DSB repair called Break-Induced Replication (BIR), the main pathway to repair broken chromosomes containing only one repairable end, which can result from the collapse of a replication fork or from telomere erosion. BIR comes at a great cost to the cell, as it promotes mutagenesis, loss of heterozygosity, translocations, and copy number variations, all hallmarks of carcinogenesis. The recent work from the lab have demonstrated that destabilizing consequences of BIR result from its unusual type of DNA synthesis driven by migrating replication bubble with asynchronous synthesis of leading and lagging strands resulting in conservative inheritance of the new genetic material. The research in the lab is supported by NIGMS

Topic

Genetic instability associated with Break Induced Replication

The repair of chromosomal double strand breaks (DSBs) is crucial in the maintenance of genomic integrity.  However, the repair of DSBs can also destabilize the genome by causing mutations and chromosomal rearrangements. Break induced replication (BIR) is one of the DSB repair pathways that proceeds by invasion of one broken end into a homologous DNA sequence followed by copying of DNA from a donor molecule all the way through its telomere.  The resulting repaired chromosome comes at a great cost to the cell, as BIR promotes mutagenesis, loss of heterozygosity, translocations, and copy number variations, all hallmarks of carcinogenesis. 

Previously we have demonstrated that the mechanism of replication during BIR is significantly different from S-phase replication, as it proceeds via an unusual bubble-like replication fork that results in conservative inheritance of the new genetic material.  This atypical mode of DNA replication is responsible for the dramatic increase in mutations associated with BIR, and also is a source of mutation clusters, similar to those associated with carcinogenesis.  We demonstrate that the impediment of DNA synthesis associated with BIR results in switch from classic BIR to microhomology-mediated break induced replication (MMBIR) leading to gross chromosomal rearrangements similar to those observed in cancer

Audience

Free and open to the university community and the public.

Host

Virginia Zakian, Department of Molecular Biology