Prof. Udi Qimron

Affiliations

Sackler School of Medicine, Tel Aviv University

Biography

Prof. Qimron completed his PhD thesis in Biology at Ben Gurion University in 2004 and his post-doctoral training at Harvard Medical School in 2009. He currently studies basic aspects of bacteriophage growth with emphasis on phage interactions with their bacterial hosts, and particularly, the recently identified bacterial defense system, the CRISPR-Cas. Prof. Qimron pioneered studies on the memorization process of the CRISPR-Cas system, and on its mechanism of action. His research also deals with novel ways to fight antibiotic-resistant bacteria.                        

Abstract

Self versus foreign discrimination by the CRISPR-Cas bacterial immune system

Udi Qimron, Rotem Sorek, Asaf Levy, Moran Goren

In the process of CRISPR adaptation, short pieces of DNA (“spacers”) are acquired from foreign elements and integrated into the CRISPR array. It so far remained a mystery how spacers are preferentially acquired from the foreign DNA while the self chromosome is avoided. Here we show that DNA breaks formed at stalled replication forks promote spacer acquisition. Chromosomal hotspots of spacer acquisition were confined by Chi sites, which are sequence octamers highly enriched on the bacterial chromosome, suggesting that these sites limit spacer acquisition from self DNA.

We further show that the avoidance of “self” is mediated by the RecBCD dsDNA break repair complex. Our results suggest that in E. coli, acquisition of new spacers depends on RecBCD-mediated processing of dsDNA breaks occurring primarily at replication stalls, and that the preference for foreign DNA is achieved through the higher density of Chi sites on the self chromosome, in combination with the higher number of forks on the foreign DNA. This model explains the strong preference to acquire spacers from both high copy plasmids and phages.