Chromosome End Repair and Genome Stability in Plasmodium falciparum
The human malaria parasite Plasmodium falciparum replicates within circulating red blood cells, where it is subjected to conditions that frequently cause DNA damage. The repair of DNA double-stranded breaks (DSBs) is thought to rely almost exclusively on homologous recombination (HR), due to a lack...
Main Authors: | , , , , , , |
---|---|
Format: | Article |
Language: | English |
Published: |
American Society for Microbiology
2017-08-01
|
Series: | mBio |
Online Access: | http://mbio.asm.org/cgi/content/full/8/4/e00547-17 |
id |
doaj-39a8580216094c5cb40b3c48cf97a531 |
---|---|
record_format |
Article |
spelling |
doaj-39a8580216094c5cb40b3c48cf97a5312021-07-02T12:57:33ZengAmerican Society for MicrobiologymBio2150-75112017-08-0184e00547-1710.1128/mBio.00547-17Chromosome End Repair and Genome Stability in Plasmodium falciparumSusannah F. CalhounJake ReedNoah AlexanderChristopher E. MasonKirk W. DeitschLaura A. KirkmanJon P. BoyleThe human malaria parasite Plasmodium falciparum replicates within circulating red blood cells, where it is subjected to conditions that frequently cause DNA damage. The repair of DNA double-stranded breaks (DSBs) is thought to rely almost exclusively on homologous recombination (HR), due to a lack of efficient nonhomologous end joining. However, given that the parasite is haploid during this stage of its life cycle, the mechanisms involved in maintaining genome stability are poorly understood. Of particular interest are the subtelomeric regions of the chromosomes, which contain the majority of the multicopy variant antigen-encoding genes responsible for virulence and disease severity. Here, we show that parasites utilize a competitive balance between de novo telomere addition, also called “telomere healing,” and HR to stabilize chromosome ends. Products of both repair pathways were observed in response to DSBs that occurred spontaneously during routine in vitro culture or resulted from experimentally induced DSBs, demonstrating that both pathways are active in repairing DSBs within subtelomeric regions and that the pathway utilized was determined by the DNA sequences immediately surrounding the break. In combination, these two repair pathways enable parasites to efficiently maintain chromosome stability while also contributing to the generation of genetic diversity.http://mbio.asm.org/cgi/content/full/8/4/e00547-17 |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Susannah F. Calhoun Jake Reed Noah Alexander Christopher E. Mason Kirk W. Deitsch Laura A. Kirkman Jon P. Boyle |
spellingShingle |
Susannah F. Calhoun Jake Reed Noah Alexander Christopher E. Mason Kirk W. Deitsch Laura A. Kirkman Jon P. Boyle Chromosome End Repair and Genome Stability in Plasmodium falciparum mBio |
author_facet |
Susannah F. Calhoun Jake Reed Noah Alexander Christopher E. Mason Kirk W. Deitsch Laura A. Kirkman Jon P. Boyle |
author_sort |
Susannah F. Calhoun |
title |
Chromosome End Repair and Genome Stability in Plasmodium falciparum |
title_short |
Chromosome End Repair and Genome Stability in Plasmodium falciparum |
title_full |
Chromosome End Repair and Genome Stability in Plasmodium falciparum |
title_fullStr |
Chromosome End Repair and Genome Stability in Plasmodium falciparum |
title_full_unstemmed |
Chromosome End Repair and Genome Stability in Plasmodium falciparum |
title_sort |
chromosome end repair and genome stability in plasmodium falciparum |
publisher |
American Society for Microbiology |
series |
mBio |
issn |
2150-7511 |
publishDate |
2017-08-01 |
description |
The human malaria parasite Plasmodium falciparum replicates within circulating red blood cells, where it is subjected to conditions that frequently cause DNA damage. The repair of DNA double-stranded breaks (DSBs) is thought to rely almost exclusively on homologous recombination (HR), due to a lack of efficient nonhomologous end joining. However, given that the parasite is haploid during this stage of its life cycle, the mechanisms involved in maintaining genome stability are poorly understood. Of particular interest are the subtelomeric regions of the chromosomes, which contain the majority of the multicopy variant antigen-encoding genes responsible for virulence and disease severity. Here, we show that parasites utilize a competitive balance between de novo telomere addition, also called “telomere healing,” and HR to stabilize chromosome ends. Products of both repair pathways were observed in response to DSBs that occurred spontaneously during routine in vitro culture or resulted from experimentally induced DSBs, demonstrating that both pathways are active in repairing DSBs within subtelomeric regions and that the pathway utilized was determined by the DNA sequences immediately surrounding the break. In combination, these two repair pathways enable parasites to efficiently maintain chromosome stability while also contributing to the generation of genetic diversity. |
url |
http://mbio.asm.org/cgi/content/full/8/4/e00547-17 |
work_keys_str_mv |
AT susannahfcalhoun chromosomeendrepairandgenomestabilityinplasmodiumfalciparum AT jakereed chromosomeendrepairandgenomestabilityinplasmodiumfalciparum AT noahalexander chromosomeendrepairandgenomestabilityinplasmodiumfalciparum AT christopheremason chromosomeendrepairandgenomestabilityinplasmodiumfalciparum AT kirkwdeitsch chromosomeendrepairandgenomestabilityinplasmodiumfalciparum AT lauraakirkman chromosomeendrepairandgenomestabilityinplasmodiumfalciparum AT jonpboyle chromosomeendrepairandgenomestabilityinplasmodiumfalciparum |
_version_ |
1721329522658246656 |