Institute seminar March 24th 10.30

Kirsten Skarstad

K. Skarstad
K. Skarstad

The institute seminar on Wednesday March 24th is given by Kirsten Skarstad from the Department of Cell Biology.

Title of her talk:
DNA replication and genome stability

The seminar takes place in the Auditorium (New Research Building Montebello) and starts at 10:30.

Abstract:

We study DNA replication, its organization and stability in simple model organisms, bacteria (and archaea). Central in our studies is molecular mechanisms, i.e. how the proteins involved work. The bacterial initiator protein is called DnaA, and is, like the archaeal ORC/Cdc6, a AAA+ type protein. It forms multimers that are capable of prying the two strands of the DNA helix apart. The strand separation also requires transcription by RNA polymerase, which under certain conditions is limiting and may time replication. The DnaA protein acts as a gene regulatory protein at several promoters. We have found that DnaA and RNA polymerase interact. This means that DnaA has two roles in initiation of replication, one as initiator and one as modulator of the transcription required for activation of the origin. The activity of DnaA is regulated by the sliding clamp which is a protein which tethers the DNA polymerase to the DNA and makes it processive. The SeqA protein also regulates initiation. It binds specifically to new, hemimethylated DNA behind the replication fork, prevents origin usage and forms large multimeric structures. Since new DNA is constantly made, SeqA must keep moving to always be on the newest DNA. Dam methylase methylates the DNA that SeqA has left. The mismatch repair protein MutH also binds hemimethylated DNA and may be part of the SeqA structure. The exact role of this structure is not clear. When DNA is damaged by for instance UV, the nucleoid changes shape and seems to form repair structures. Repair structures involving recombination proteins may also be formed when replication forks collapse and are re-built.

Links:

Home page of Kirsten Skarstad's group - Regulation of DNA replication.

Department of Cell Biology

Institute for Cancer Research

Institute seminars, spring 2010