Chaired by Amar Klar, NCI

Main Auditorium, Natcher Conference Center

DNA replication of a chromosome produces chemically identical, duplicate copies, called sister chromatids.  They are generally thought to be randomly distributed to daughter cells. However, because of the semi-conservative nature of DNA replication and according to the Watson and Crick double-helix structure, the sister chromatids differ both in the age of DNA chains and in the Watson versus Crick DNA chain sequence.  Consequently, two nonrandom and one random distribution possibilities exist when considering the age patterns of chromatids copied and segregated from the two chromosome homologs. Cairns (1975) postulated biased delivery of the "oldest" DNA strands to asymmetrically dividing self-renewing stem cells to avoid inheriting cancer-causing DNA replication errors.  Another somatic strand-specific imprinting and patterned segregation (SSIS) model was proposed to explain visceral laterality development, whereby visceral organs, such as heart, lungs, liver, and kidneys are asymmetrically placed on the left-right (LR) body axis in mice as well as for human brain hemispheres lateralization concerning human left versus right hand-use preference and anomalies of brain laterality which cause schizophrenia and bipolar disorders (Klar 2002).  By hypothesis, chromosome replication produces developmentally non-equivalent sister chromatids by epigenetic mechanisms.  As a consequence of biased segregation of biased strand/chromatid distribution, daughters would have been modified in a manner that would differentially regulate the pattern of gene expression in them and in their progeny.  The SSIS model proposes chromosome-specific nonrandom sorting of DNA chains as a mechanism for cellular differentiation, while the Cairns model proposes the genome-wide "immortal" strand inheritance in stem cells to avoid DNA replication errors that in future may cause cancer development.  Both models have received considerable recent support.  Such nonrandom strand distribution perhaps derives from nonrandom placement of chromosomes in nuclear space.  The investigators actively working in this budding field will be brought together to exchange ideas, share progress, promote collaborations and to expose NIH workers to research of this budding field that is bound to explode in the next few years.

Program:

Asymmetric DNA Segregation during Mammary Gland Development and Differentiation in the Mouse
Gilbert H. Smith, NCI

The Phenomenon of Selective versus Random DNA Strand Segregation in Mouse Cell Mitosis
Amar J. Klar, NCI

Tissue-specific Organization of Genomes
Tom Misteli, NCI