Establishing a biochemical understanding of the initiation of chromosome replication in bacteria.

In the mid-1950s, Arthur Kornberg elucidated the enzymatic synthesis of DNA by DNA polymerase, for which he was recognized with the 1959 Nobel Prize in Physiology or Medicine. He then identified many of the proteins that cooperate with DNA polymerase to replicate duplex DNA of small bacteriophages. However, one major unanswered problem was understanding the mechanism and control of the initiation of chromosome replication in bacteria.

Origins of DNA replication in eukaryotes.

Errors occurring during DNA replication can result in inaccurate replication, incomplete replication, or re-replication, resulting in genome instability that can lead to diseases such as cancer or disorders such as autism. A great deal of progress has been made toward understanding the entire process of DNA replication in eukaryotes, including the mechanism of initiation and its control. This review focuses on the current understanding of how the origin recognition complex (ORC) contributes to determining the location of replication initiation in the multiple chromosomes within eukaryotic cells, as well as methods for mapping the location and temporal patterning of DNA replication.

Prevalent and dynamic binding of the cell cycle checkpoint kinase Rad53 to gene promoters.

Replication of the genome must be coordinated with gene transcription and cellular metabolism, especially following replication stress in the presence of limiting deoxyribonucleotides. The Rad53 (CHEK2 in mammals) checkpoint kinase plays a major role in cellular responses to DNA replication stress. Cell cycle regulated, genome-wide binding of Rad53 to chromatin was examined.

Pelvic floor behavioral treatment for fecal incontinence and constipation in quiescent inflammatory bowel disease.

Background And Aim: Refractory bowel symptoms in quiescent inflammatory bowel disease (IBD) are common but evidence for effective management is limited. We aimed to determine whether behavioral treatment, including pelvic floor muscle training, decreases the severity of functional bowel symptoms in patients with quiescent IBD. Secondary aims were to evaluate the treatment effect on quality of life, psychological well-being and pelvic floor muscle function.

The remarkable gymnastics of ORC.

As a cell prepares to divide, a molecular actor known as the Origin Recognition Complex makes intricate ATP-driven movements to recruit proteins required to duplicate DNA.