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| Content Provider | PubMed Central |
|---|---|
| Author | Erliandri, Indri Fu, Haiqing Nakano, Megumi Kim, Jung-hyun Miga, Karen H. Mikhail, Liskovykh Earnshaw, William C. Masumoto, Hiroshi Kouprina, Natalay Aladjem, Mirit I. Larionov, Vladimir |
| Copyright Year | 2014 |
| Abstract | In human chromosomes, centromeric regions comprise megabase-size arrays of 171 bp alpha-satellite DNA monomers. The large distances spanned by these arrays preclude their replication from external sites and imply that the repetitive monomers contain replication origins. However, replication within these arrays has not previously been profiled and the role of alpha-satellite DNA in initiation of DNA replication has not yet been demonstrated. Here, replication of alpha-satellite DNA in endogenous human centromeric regions and in de novo formed Human Artificial Chromosome (HAC) was analyzed. We showed that alpha-satellite monomers could function as origins of DNA replication and that replication of alphoid arrays organized into centrochromatin occurred earlier than those organized into heterochromatin. The distribution of inter-origin distances within centromeric alphoid arrays was comparable to the distribution of inter-origin distances on randomly selected non-centromeric chromosomal regions. Depletion of CENP-B, a kinetochore protein that binds directly to a 17 bp CENP-B box motif common to alpha-satellite DNA, resulted in enrichment of alpha-satellite sequences for proteins of the ORC complex, suggesting that CENP-B may have a role in regulating the replication of centromeric regions. Mapping of replication initiation sites in the HAC revealed that replication preferentially initiated in transcriptionally active regions. |
| Related Links | http://dx.doi.org/10.1093/nar/gku835 |
| Ending Page | 11516 |
| Page Count | 15 |
| Starting Page | 11502 |
| File Format | |
| ISSN | 13624962 |
| e-ISSN | 13624962 |
| Journal | Nucleic Acids Research |
| Issue Number | 18 |
| Volume Number | 42 |
| Language | English |
| Publisher | Oxford University Press |
| Publisher Date | 2014-10-13 |
| Access Restriction | Open |
| Rights Holder | Oxford University Press |
| Subject Keyword | Research in Higher Education |
| Content Type | Text |
| Resource Type | Article |
| Subject | Genetics |
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