Current advances in unraveling the function of the Werner syndrome protein.
Werner syndrome (WS) is an autosomal recessive premature aging disease manifested by the mimicry of age-related phenotypes such as atherosclerosis, arteriosclerosis, cataracts, osteoporosis, soft tissue calcification, premature thinning, graying, and loss of hair, as well as a high incidence of some types of cancers. The gene product defective in WS, WRN, is a member of the RecQ family of DNA helicases that are widely distributed in nature and believed to play central roles in genomic stability of organisms ranging from prokaryotes to mammals. Interestingly, WRN is a bifunctional protein that is exceptional among RecQ helicases in that it also harbors an exonuclease activity. Furthermore, it preferentially operates on aberrant DNA structures believed to exist in vivo as intermediates in specific DNA transactions such as replication (forked DNA), recombination (Holliday junction, triplex and tetraplex DNA), and repair (partial duplex with single stranded bubble). In addition, WRN has been shown to physically and functionally interact with a variety of DNA-processing proteins, including those that are involved in resolving alternative DNA structures, repair DNA damage, and provide checkpoints for genomic stability. Despite significant research activity and considerable progress in understanding the biochemical and molecular genetic function of WRN, the in vivo molecular pathway(s) of WRN remain elusive. The following review focuses on the recent advances in the biochemistry of WRN and considers the putative in vivo functions of WRN in light of its many protein partners.
Ozgenc
Ali
A
The Joseph Gottstein Memorial Cancer Research Laboratory, Department of Pathology, University of Washington, Seattle, WA 98195-7705, USA.
Loeb
Lawrence A
LA
D004265:DNA Helicases / Q000502:physiology*; D005090:Exodeoxyribonucleases; D006801:Humans; D053484:RecQ Helicases; D014898:Werner Syndrome / Q000503:physiopathology*; D000071657:Werner Syndrome Helicase
D005090:Exodeoxyribonucleases; D004265:DNA Helicases; D053484:RecQ Helicases; C098785:WRN protein, human; D000071657:Werner Syndrome Helicase