Core of a chromosome

The secret chromosome center, the root of many cancers, is sequenced

Published: Thursday 15 November 2001

when the human genome was sequenced, everyone kept the lid down on the dark secret of genomics -- the sequencers hadn't touched the hearts of the chromosomes. Now, at last, one chromosome's inscrutable midpoint, its centromere, has been peered into and its genetic secrets revealed.

Centromeres look like the 'waist' portion of the alphabet x. They share out chromosomes fairly when a cell divides. Defective centromeres may underlie many cancers, in which problems with chromosome movement at cell division are common. Unfortunately, repetitive sections in these regions confuse genome supercomputers -- it's like struggling with an expanse of blue sky in a huge jigsaw puzzle.

"It's taken 15-20 years in diffe-rent organisms to chase down," says Huntington Willard of Case Western Reserve University in Cleveland, Ohio, usa.

The centromere consists of a recurring 171-letter sequence, called alpha satellite dna. The team used the rare differences between one repeat and the next to fit them together. "It's like leading yourself hand over hand by a rope," says Willard. Three million letters of these repeats is enough to make a working centromere, they show, proving that they've identified the real thing.

The group also compared sequences that bookend the alpha repeats with equivalent sections in primates. One part of an ancestral primate centromere is amplified in humans, they found.

The work gives a clear picture of how the centromere might have evolved. Even with the sequence in hand, no one knows how centromeres work. Unlike genes, which tend to be similar between organisms, centromeres are totally different in yeast, plants and flies. This suggests that the sequence itself is not very important. How the dna is packaged with proteins into a three-dimensional structure may make the centromere what it is.

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