Here, we address the role of the MRN (Mre11/Rad50/Nbs1) complex in the response to telomeres rendered dysfunctional by deletion of the shelterin component TRF2. Using conditional NBS1/TRF2 double-knockout MEFs, we show that MRN is required for ATM signaling in response to telomere dysfunction. This establishes that MRN is the only sensor for the ATM kinase and suggests that TRF2 might block ATM...

Multiple myeloma (MM) is a hematological malignancy characterized by frequent chromosome abnormalities. However, the molecular basis for this genome instability remains unknown. Since both impaired and hyperactive double strand break (DSB) repair pathways can result in DNA rearrangements, we investigated the functionality of DSB repair in MM cells. Repair kinetics of ionizing-radiation (IR)-ind...

Retinal post-mitotic neurocytes display genomic instability after damage induced by physiological or pathological factors. The involvement of BRCA1, an important factor in development and DNA repair in mature retinal neurocytes remains unclear. Thus, we investigated the developmental expression profile of BRCA1 in the retina and defined the role of BRCA1 in DNA repair in retinal neurocytes. Our...

The prevention of nonhomologous end-joining (NHEJ) reactions between chromosome ends is crucial for maintaining genome stability. Although this protective function is known to be fulfilled by a core of conserved telomeric proteins that are collectively known as Shelterin, its mechanistic details remain a mystery. In this issue, Sarthy et al (2009) lend fresh insight by developing an ingenious m...

DNA repair efficiency is an important determinant of oocyte quality and female fertility. DYNLL1 (Dynein light chain 1) plays a part in double-strand break (DSB) choice by promoting error-prone non-homologous end joining (NHEJ) contrast limiting accurate error-free homologous recombination (HR) repair. Here, we showed that transcript abundance decreases gradually during follicular growth mice. ...

Chromosomal double stranded breaks (DSBs) are regarded as the most cytotoxic form of DNA damage, and occur as a result of normal cellular processes, such as DNA replication, as well as in response to ionizing radiation, and chemotherapeutics. These breaks must be repaired to ensure genomic stability and viability. In vertebrates, nonhomologous end joining (NHEJ) is the main pathway for repair o...

human embryonic stem cells (hESCs) are able to differentiate in all different specialized tissues [1]. Yet, as all living cells, they have to cope with endogenous or exogenous DNA damage. Their efficacy in DNA repair is somewhat controversial. Clearly hESCs can achieve the indispensable genome stability either by more effective repair or, on the contrary, by increasing apoptosis thus eliminatin...

In yeast, the nonhomologous end joining pathway (NHEJ) mobilizes the DNA polymerase Pol4 to repair DNA double-strand breaks when gap filling is required prior to ligation. Using telomere-telomere fusions caused by loss of the telomeric protein Rap1 and double-strand break repair on transformed DNA as assays for NHEJ between fully uncohesive ends, we show that Pol4 is able to extend a 3'-end who...

The telomeres of eukaryotes are stable open double-strand ends that coexist with nonhomologous end joining (NHEJ), the repair pathway that directly ligates DNA ends generated by double-strand breaks. Since a single end-joining event between 2 telomeres generates a circular chromosome or an unstable dicentric chromosome, NHEJ must be prevented from acting on telomeres. Multiple mechanisms mediat...

The role of the familial breast cancer susceptibility genes, BRCA1 and BRCA2, in the homologous recombination pathway for DNA double-strand break (DSB) repair suggests that the mechanisms involved in DNA DSB repair are of particular etiological importance during breast tumorigenesis. However, there is currently no evidence for an association between breast cancer and the other DSB repair pathwa...