Expansion of human centromeric arrays in cells undergoing break-induced replication.
Cell Rep
; 43(3): 113851, 2024 Mar 26.
Article
en En
| MEDLINE
| ID: mdl-38427559
ABSTRACT
Human centromeres are located within α-satellite arrays and evolve rapidly, which can lead to individual variation in array length. Proposed mechanisms for such alterations in length are unequal crossover 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 â¼20 somatic cell divisions of an alternative lengthening of telomere (ALT)-positive cell line. We find that the frequency of array variation among single-cell-derived subclones ranges from a minimum of â¼7% to a maximum of â¼100%. 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.
Palabras clave
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
ADN Satélite
/
Centrómero
Límite:
Humans
Idioma:
En
Revista:
Cell Rep
Año:
2024
Tipo del documento:
Article
País de afiliación:
Estados Unidos
Pais de publicación:
Estados Unidos