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Is DNA damage response ready for action anywhere?

Terradas M, Martín M, Hernández L, Tusell L, Genescà A - Int J Mol Sci (2012)

Bottom Line: This response has to be rapid and accurate in order to keep genome integrity.In this review, we have collected data regarding the presence of DDR factors on micronuclear DNA lesions that indicate that micronuclei are almost incapable of generating an effective DDR because of defects in their nuclear envelope.Finally, considering the recent observations about the reincorporation of micronuclei to the main bulk of chromosomes, we suggest that, under certain circumstances, micronuclei carrying DNA damage might be a source of chromosome instability.

View Article: PubMed Central - PubMed

Affiliation: Department of Cell Biology, Physiology and Immunology, Universitat Autònoma de Barcelona, 08193 Bellaterra (Cerdanyola del Vallès), Spain; E-Mails: marta.martin@uab.cat (M.M.); laia.hernandez@uab.cat (L.H.); laura.tusell@uab.cat (L.T.); anna.genesca@uab.cat (A.G.).

ABSTRACT
Organisms are continuously exposed to DNA damaging agents, consequently, cells have developed an intricate system known as the DNA damage response (DDR) in order to detect and repair DNA lesions. This response has to be rapid and accurate in order to keep genome integrity. It has been observed that the condensation state of chromatin hinders a proper DDR. However, the condensation state of chromatin is not the only barrier to DDR. In this review, we have collected data regarding the presence of DDR factors on micronuclear DNA lesions that indicate that micronuclei are almost incapable of generating an effective DDR because of defects in their nuclear envelope. Finally, considering the recent observations about the reincorporation of micronuclei to the main bulk of chromosomes, we suggest that, under certain circumstances, micronuclei carrying DNA damage might be a source of chromosome instability.

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Related in: MedlinePlus

Model relating the structure and functionality of the nuclear envelope to the import of XPC (Xeroderma pigmentosum group C) into the micronucleus: Diagram of the structure of the micronuclear envelope (left); Double nuclear pore complexes (NPC)/XPC immunofluorescence carried out in our laboratory (right). (A) Micronucleus with a proper envelope labeled with both NPC and XPC. (B) Micronucleus with dysfunctional NPCs labeled with NPC but it does not show XPC labeling. (C) Micronucleus lacking NPCs and, in some cases, without lamina as it does not display either NPC nor XPC.
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f2-ijms-13-11569: Model relating the structure and functionality of the nuclear envelope to the import of XPC (Xeroderma pigmentosum group C) into the micronucleus: Diagram of the structure of the micronuclear envelope (left); Double nuclear pore complexes (NPC)/XPC immunofluorescence carried out in our laboratory (right). (A) Micronucleus with a proper envelope labeled with both NPC and XPC. (B) Micronucleus with dysfunctional NPCs labeled with NPC but it does not show XPC labeling. (C) Micronucleus lacking NPCs and, in some cases, without lamina as it does not display either NPC nor XPC.

Mentions: To determine whether the low presence of DDR factors in micronuclei is a consequence of defects in the micronuclear envelope, the presence of nucleoporines (rich in FXFG repeats) and lamin B1 in radiation-induced micronuclei was analyzed by immunofluorescence assay [54]. While the main part of micronuclei showed lamin B1, only 30% of them exhibited nucleoporines. This result pointed to the absence of nucleoporines as the main cause of import defects, which was finally demonstrated when the presence of XPC and nucleoporines was analyzed in the same experiment and no XPC positive micronucleus was devoid of nucleoporines. In any case, some micronuclei showing nucleoporines were XPC negative, suggesting that the NPCs detected at these micronuclei were dysfunctional (Figure 2).


Is DNA damage response ready for action anywhere?

Terradas M, Martín M, Hernández L, Tusell L, Genescà A - Int J Mol Sci (2012)

Model relating the structure and functionality of the nuclear envelope to the import of XPC (Xeroderma pigmentosum group C) into the micronucleus: Diagram of the structure of the micronuclear envelope (left); Double nuclear pore complexes (NPC)/XPC immunofluorescence carried out in our laboratory (right). (A) Micronucleus with a proper envelope labeled with both NPC and XPC. (B) Micronucleus with dysfunctional NPCs labeled with NPC but it does not show XPC labeling. (C) Micronucleus lacking NPCs and, in some cases, without lamina as it does not display either NPC nor XPC.
© Copyright Policy - open-access
Related In: Results  -  Collection

License 1 - License 2
Show All Figures
getmorefigures.php?uid=PMC3472763&req=5

f2-ijms-13-11569: Model relating the structure and functionality of the nuclear envelope to the import of XPC (Xeroderma pigmentosum group C) into the micronucleus: Diagram of the structure of the micronuclear envelope (left); Double nuclear pore complexes (NPC)/XPC immunofluorescence carried out in our laboratory (right). (A) Micronucleus with a proper envelope labeled with both NPC and XPC. (B) Micronucleus with dysfunctional NPCs labeled with NPC but it does not show XPC labeling. (C) Micronucleus lacking NPCs and, in some cases, without lamina as it does not display either NPC nor XPC.
Mentions: To determine whether the low presence of DDR factors in micronuclei is a consequence of defects in the micronuclear envelope, the presence of nucleoporines (rich in FXFG repeats) and lamin B1 in radiation-induced micronuclei was analyzed by immunofluorescence assay [54]. While the main part of micronuclei showed lamin B1, only 30% of them exhibited nucleoporines. This result pointed to the absence of nucleoporines as the main cause of import defects, which was finally demonstrated when the presence of XPC and nucleoporines was analyzed in the same experiment and no XPC positive micronucleus was devoid of nucleoporines. In any case, some micronuclei showing nucleoporines were XPC negative, suggesting that the NPCs detected at these micronuclei were dysfunctional (Figure 2).

Bottom Line: This response has to be rapid and accurate in order to keep genome integrity.In this review, we have collected data regarding the presence of DDR factors on micronuclear DNA lesions that indicate that micronuclei are almost incapable of generating an effective DDR because of defects in their nuclear envelope.Finally, considering the recent observations about the reincorporation of micronuclei to the main bulk of chromosomes, we suggest that, under certain circumstances, micronuclei carrying DNA damage might be a source of chromosome instability.

View Article: PubMed Central - PubMed

Affiliation: Department of Cell Biology, Physiology and Immunology, Universitat Autònoma de Barcelona, 08193 Bellaterra (Cerdanyola del Vallès), Spain; E-Mails: marta.martin@uab.cat (M.M.); laia.hernandez@uab.cat (L.H.); laura.tusell@uab.cat (L.T.); anna.genesca@uab.cat (A.G.).

ABSTRACT
Organisms are continuously exposed to DNA damaging agents, consequently, cells have developed an intricate system known as the DNA damage response (DDR) in order to detect and repair DNA lesions. This response has to be rapid and accurate in order to keep genome integrity. It has been observed that the condensation state of chromatin hinders a proper DDR. However, the condensation state of chromatin is not the only barrier to DDR. In this review, we have collected data regarding the presence of DDR factors on micronuclear DNA lesions that indicate that micronuclei are almost incapable of generating an effective DDR because of defects in their nuclear envelope. Finally, considering the recent observations about the reincorporation of micronuclei to the main bulk of chromosomes, we suggest that, under certain circumstances, micronuclei carrying DNA damage might be a source of chromosome instability.

Show MeSH
Related in: MedlinePlus