Searching DNA in 3D

ells with shortening telomeres hit two successive barriers: they first stop dividing as they become senescent, and later undergo a cell death process termed crisis. Although crisis may, as suggested by others, be controlled by overall telomere length, and colleagues now blame the onset of senescence on a particular structure at the end of telomeres. The important structure is a single-stranded overhang of G-rich residues at the 3 Ј end. The group demonstrates that overhang length of several hundred bases is maintained over many generations of cell divisions, but drops to fewer than 100 residues at senescence. Telomerase increased overhang length, which may account for its ability to delay senescence. Various cellular stresses caused minor shortening of the overhang—cumulative stresses may therefore shorten it sufficiently to initiate senescence. Cells with inactivated p53 and Rb tumor suppressor pathways continued to divide despite loss of overhangs, suggesting that these cells are resistant to the putative growth inhibitory effects of overhang loss. Weinberg says the results indicate " the function of telomeres is unrelated to calculating the number of cell divisions. Instead, they represent signal transducing devices " that detect cellular stresses. The overhang is critical for forming the T-loop, which prevents end-to-end chromosome joining. Short overhangs may disrupt the T-loop, or another aspect of telomere structure, which may lead to release of a DNA damage signal that initiates p53 and Rb signaling. ᭿ Ring around the chromatin ew insight into the structure of cohesin suggests it might lasso sister chromatids to hold them together until anaphase. report interactions between cohesin subunits that reveal a circular structure for the complex. The ring consists of cohesin subunits Smc1, Smc3, and Scc1. Previous results indicated that Smc heterodimers form a V-shape, with the two proteins joined at the hinge. Now, immunoprecipitation experiments demonstrate that the ends of the V are joined by Scc1 (or by its meiotic replacement, Rec8), forming a ring of cohesin on chromatin in vivo. N Cleavage of the ring by separase released the it from chromatin in vitro and in vivo. " The big question now, " says Nasmyth, " is what is the pathway of the DNA. Is it trapped inside the ring? " Although he has not yet seen sister Cohesin rings hold chromatids together until the ring is cleaved at anaphase. Nasmyth chromatids within a single ring, the ring size is estimated to be about four times the …