Dr. Carl Schildkraut schildkr at aecom.yu.edu
Sat Dec 12 18:48:40 EST 1998



        	A position is available to study the molecular genetics of
replication and the cell cycle in the mammalian genome.  Our laboratory
has been studying the replication of the immunoglobulin heavy chain
(Igh) gene locus in mouse and human cell lines.  In a non-B cell line
in which immunoglobulin genes are not expressed, we have identified a
region of about 50 kb in which replication of the Igh locus initiates (
Mol. Cell. Biol. 17:6167, 1997; Mol. Cell , 1999 in press).  We now
plan to focus on this initiation region and determine if it is a
sequence specific initiation site.  The evidence we have thus far
indicates that this is a very important site replication initiation
site.  We plan to determine whether the mammalian Origin Recognition
Complex (ORC) binds to this site and to determine whether there is a
pre-replication complex at this site.  Importantly, we have
demonstrated for the first time in mammalian cells that a gradual
transition between early and a late replicated domains in the Igh locus
is achieved by a single replication fork.  This raises the possibility
that the transition between other early and late replicating regions is
also achieved in this manner.

        In preB cell lines, we are identifying a developmentally
regulated replication origin for the Igh locus that appears to be used
only when the locus is expressed.  Using this system we plan to
determine whether ORC binds to the same sequences in MEL cells and pre
B cells even if the origins of DNA replication are silent in MEL cells.
 We will also determine whether specific proteins in cells of the B
lineage play a role in regulating usage of this developmentally
regulated replication origin, possibly by interacting with ORC in the
pre-replication complex.

        We also use the Epstein-Barr virus genome as a model system for
replication of the human and mouse genomes  (Cell 58:527, 1989; Mol.
Cell. Biol. 15:2893, 1995).   We are developing an approach to use
fluorescent antibodies to study initiation in pure populations of
isolated EBV genomes.  We will then use this approach to focus on the
developmentally regulated replication origin in cells of the B lineage.
 We will use the EBV genome as well as the Igh locus to determine
whether ORC binds to mammalian replication origins. 

Send curriculum vitae by both Email and FAX or Air Mail and the names
of three references (including telephone, FAX and Email numbers) to: 

     Dr. Carl Schildkraut, Professor
     Department of Cell Biology (CH 416)
     Albert Einstein College of Medicine
     1300 Morris Park Ave.
     New York, New York  10461

	Phone (718)  430-2097
	FAX   (718)  430-8574
	Email   schildkr at aecom.yu.edu

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