DNA non-homologous end joining (NHEJ) and homologous recombination (HR) function to repair DNA double-strand breaks (DSBs) in G2 phase with HR preferentially repairing heterochromatin-associated DSBs (HC-DSBs). Here, we examine the regulation of repair pathway usage at two-ended DSBs in G2. We identify the speed of DSB repair as a major component… (More)
Mammalian cells repair DNA double-strand breaks (DSBs) through either homologous recombination or non-homologous end joining (NHEJ). V(D)J recombination, a cut-and-paste mechanism for generating diversity in antigen receptors, relies on NHEJ for repairing DSBs introduced by the Rag1-Rag2 protein complex. Animals lacking any of the seven known NHEJ factors… (More)
XRCC4 and XLF are structurally related proteins important for DNA Ligase IV function. XRCC4 forms a tight complex with DNA Ligase IV while XLF interacts directly with XRCC4. Both XRCC4 and XLF form homodimers that can polymerize as heterotypic filaments independently of DNA Ligase IV. Emerging structural and in vitro biochemical data suggest that XRCC4 and… (More)
Potential roles of the abasic site lyase activity associated with AlkB homolog 1 (ALKBH1) were assessed by studies focusing on the two cellular processes that create abasic sites as intermediates: base excision repair and class switch recombination. Alkbh1(-/-) pups (lacking exon 3) were born at a lower than expected frequency from heterozygous parents,… (More)
DNA-PK is a protein complex that consists of a DNA-binding, regulatory subunit [Ku] and a larger approximately 465 kDa catalytic subunit [DNA-PKcs], a serine/threonine protein kinase. The kinase activity of DNA-PKcs resides between residues 3745 and 4013, a PI3 kinase domain. Another recognized domain within this large protein is a leucine zipper (LZ) motif… (More)
The DNA-dependent protein kinase (DNA-PK) was identified as an activity and as its three component polypeptides 25 and 15 years ago, respectively. It has been exhaustively characterized as being absolutely dependent on free double stranded DNA ends (to which it is directed by its regulatory subunit, Ku) for its activation as a robust nuclear… (More)
It is now evident that most if not all major intrastrain crossreactive idiotypes (CRI) I result from the expression of unmutated germline genes or germline genes that have undergone a moderate degree of somatic mutation (1-1 1). The association with germline genes can account for the ubiquitous presence of such idiotypes within a strain (12), as contrasted… (More)
To optimize night vision, nocturnal mammals exploit the light refractive properties of heterochromatin, adopting a unique nuclear structure that positions heterochromatin at the center of the nucleus focusing light on photoreceptors. This strategy comes at the expense of genome protection because DNA breaks cannot be repaired in dense heterochromatin.