Expansion of human centromeric arrays in cells undergoing break-induced replication.
Journal
bioRxiv : the preprint server for biology
Titre abrégé: bioRxiv
Pays: United States
ID NLM: 101680187
Informations de publication
Date de publication:
15 Nov 2023
15 Nov 2023
Historique:
pubmed:
28
11
2023
medline:
28
11
2023
entrez:
28
11
2023
Statut:
epublish
Résumé
Human centromeres are located within α-satellite arrays and evolve rapidly, which can lead to individual variation in array lengths. Proposed mechanisms for such alterations in lengths are unequal cross-over between sister chromatids, gene conversion, and break-induced replication. However, the underlying molecular mechanisms responsible for the massive, complex, and homogeneous organization of centromeric arrays have not been experimentally validated. Here, we use droplet digital PCR assays to demonstrate that centromeric arrays can expand and contract within ~20 somatic cell divisions of a cell line. We find that the frequency of array variation among single-cell-derived subclones ranges from a minimum of ~7% to a maximum of ~100%. Further clonal evolution revealed that centromere expansion is favored over contraction. We find that the homologous recombination protein RAD52 and the helicase PIF1 are required for extensive array change, suggesting that centromere sequence evolution can occur via break-induced replication.
Identifiants
pubmed: 38014305
doi: 10.1101/2023.11.11.566714
pmc: PMC10680626
pii:
doi:
Types de publication
Preprint
Langues
eng
Subventions
Organisme : NIGMS NIH HHS
ID : R35 GM150532
Pays : United States
Commentaires et corrections
Type : UpdateIn
Déclaration de conflit d'intérêts
DECLARATION OF INTERESTS The authors declare no competing interests.
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