The end replication problem in linear chromosomes. Just two rounds of chromosome replication are shown here. In the first generation of replication (left; red indicates new DNA), lagging-strand synthesis results in an RNA primer at or near one 5′ end of each new chromosome. After removal of the RNA, the 5′ single-strand gap in the DNA cannot be filled, thus a 3′ single-stranded DNA overhang remains. In the second generation (right; yellow indicates new DNA), each first-generation chromosome produces two new chromosomes, for a total of four new duplexes. Two of the new chromosomes have lost DNA at one end. All four chromosomes terminate with a 5′ single-strand gap in the DNA after the RNA is removed. Further losses will be sustained with each new generation.