Anna Malkova (University of Iowa)

Genetic instability associated with Break Induced Replication
Nov 21, 2016, 12:00 pm12:00 pm
Thomas Laboratory, 003
Free and open to the university community and the public.


Anna Malkova
University of Iowa


Event Description

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

Virginia Zakian, Department of Molecular Biology
Event Category
Butler Seminar Series