Editing Telomere (section)

=== End replication problem ===
{{Main|DNA replication}} 
[[File:Dnareplication.svg|thumb|250 px|Lagging strand during DNA replication]]

During DNA replication, [[DNA polymerase]] cannot replicate the sequences present at the [[Directionality (molecular biology)|3' ends]] of the parent strands. This is a consequence of its unidirectional mode of DNA synthesis: it can only attach new nucleotides to an existing 3'-end (that is, synthesis progresses 5'-3') and thus it requires a [[Primer (molecular biology)|primer]] to initiate replication. On the leading strand (oriented 5'-3' within the replication fork), DNA-polymerase continuously replicates from the point of initiation all the way to the strand's end with the primer (made of [[RNA]]) then being excised and substituted by DNA. The lagging strand, however, is oriented 3'-5' with respect to the replication fork so continuous replication by DNA-polymerase is impossible, which necessitates discontinuous replication involving the repeated synthesis of primers further 5' of the site of initiation (see [[lagging strand|lagging strand replication]]). The last primer to be involved in lagging-strand replication sits near the 3'-end of the template (corresponding to the potential 5'-end of the lagging-strand). Originally it was believed that the last primer would sit at the very end of the template, thus, once removed, the DNA-polymerase that substitutes primers with DNA (DNA-Pol δ in eukaryotes){{refn|group=note|name=note1|During replication, multiple DNA-polymerases are involved.}} would be unable to synthesize the "replacement DNA" from the 5'-end of the lagging strand so that the template nucleotides previously paired to the last primer would not be replicated.<ref>{{cite journal |vauthors=Olovnikov AM |title=A theory of marginotomy. The incomplete copying of template margin in enzymic synthesis of polynucleotides and biological significance of the phenomenon |journal=Journal of Theoretical Biology |volume=41 |issue=1 |pages=181–90 |date=September 1973 |pmid=4754905 |doi=10.1016/0022-5193(73)90198-7 |bibcode=1973JThBi..41..181O}}</ref> It has since been questioned whether the last lagging strand primer is placed exactly at the 3'-end of the template and it was demonstrated that it is rather synthesized at a distance of about 70–100 nucleotides which is consistent with the finding that DNA in cultured human cell is shortened by 50–100 [[base pair]]s per [[cell division]].<ref>{{cite journal |vauthors=Chow TT, Zhao Y, Mak SS, Shay JW, Wright WE |title=Early and late steps in telomere overhang processing in normal human cells: the position of the final RNA primer drives telomere shortening |journal=Genes & Development |volume=26 |issue=11 |pages=1167–1178 |date=June 2012 |pmid=22661228 |pmc=3371406 |doi=10.1101/gad.187211.112}}</ref>

If coding sequences are degraded in this process, potentially vital genetic code would be lost. Telomeres are non-coding, repetitive sequences located at the termini of linear chromosomes to act as buffers for those coding sequences further behind. They "cap" the end-sequences and are progressively degraded in the process of DNA replication.

The "end replication problem" is exclusive to linear chromosomes as circular chromosomes do not have ends lying without reach of DNA-polymerases. Most [[prokaryote]]s, relying on circular chromosomes, accordingly do not possess telomeres.<ref>{{Cite book |first1=David L. |last1=Nelson |first2=Albert L. |last2=Lehninger |first3=Michael M. |last3=Cox |name-list-style=vanc |title=Lehninger Principles of Biochemistry |date=2008|publisher=W.H. Freeman |isbn=9780716771081 |edition=5th |location=New York |oclc=191854286 |url-access=registration |url=https://archive.org/details/lehningerprincip00lehn_1}}</ref> A small fraction of [[bacteria]]l chromosomes (such as those in ''[[Streptomyces]]'', ''[[Agrobacterium]]'', and ''[[Borrelia]]''), however, are linear and possess telomeres, which are very different from those of the eukaryotic chromosomes in structure and function. The known structures of bacterial telomeres take the form of [[proteins]] bound to the ends of linear chromosomes, or hairpin loops of single-stranded DNA at the ends of the linear chromosomes.<ref>{{cite web |url= http://www.sci.sdsu.edu/~smaloy/MicrobialGenetics/topics/chroms-genes-prots/chromosomes.html |title=Bacterial Chromosome Structure |last=Maloy|first=Stanley |name-list-style=vanc |date=July 12, 2002 |access-date=2008-06-22}}</ref>