CH385: Unit 1

DNA repair

a set of different enzymatic processes for repairing the many accidental lesions that occur continually in DNA.

depurination

the removal of a purine base (A/G) from DNA

deamination

the removal of an amino group from an amino acid

base excision repair

DNA repair pathway in which single faulty bases are removed from the DNA helix and replaced

nuelcotide excision repair

type of DNA repair that corrects irreversible damage of the DNA double helix, such as that caused by certain chemicals or UV light, by cutting out the damaged region on one strand and resynthesizing it using the undamaged strand as template

DNA glycosylase

first step in base excision repair, it recognizes and removes a damaged/incorrect nitrogenous base from the strand

translesion polymerase

specialized enzymes that allow DNA replication to continue past damaged sites, plays a crucial role in DNA damage tolerance

nonhomologous end joining

a DNA repair mechanism for rejoining the ends at double-strand breaks in which the two broken ends of DNA are brought together and rejoined by DNA ligation, generally with the loss of one or more nucleotides at the site of joining.

homologous recombination

genetic exchange between a pair of identical or very similar DNA sequences, often those located on two copies of the same chromosome. Provides an error-free mechanism for repairing DNA double-strand breaks

hybridization

process whereby two complementary nucleic acid strands form a base-paired duplex DNA–DNA, DNA–RNA, or RNA–RNA molecule. Forms the basis of a powerful technique for detecting specific nucleotide sequences

strand exchange

reaction in which a single-strand 3′ end from one duplex DNA molecule penetrates another duplex and finds a homologous sequence through base-pairing

RecA/Rad51

prototype for a ubiquitous class of DNA-binding proteins that catalyze synapsis of DNA strands during genetic recombination in bacteria; analogous to Rad51 protein in eukaryotes, where it catalyzes pairing of homologous DNA strands during recombination and repair processes

alleles

one of several alternative forms of a gene

crossing over

exchange of genetic material between non-sister chromatids of homologous chromosomes during meiosis, resulting in new combinations of alleles and increased genetic diversity

gene

region of DNA that is transcribed as a single unit and carries information for a discrete hereditary characteristic

deoxyribonucleic acid

polynucleotide formed from covalently linked deoxyribonucleotide units. The store of hereditary information within a cell and the carrier of this information

double helix

the 3D structure of DNA, in which two antiparallel DNA chains, held together by hydrogen-bonding between the bases, are wound into a helix

base pairs

a pair of complementary bases in a double-stranded nucleic acid molecule, consisting of a purine in one strand linked by HYDROGEN bonds to a pyridine in another (AT has 2 bonds, CG has 3) think: T for two, C and G rhyme with 3

antiparallel

describes the relative orientation of the two strands in a DNA double helix or two paired regions of a polypeptide chain; the chemical polarity of one strand is opposite to that of the other (5’ to 3’ and 3’ to 5’)

template

single strand of DNA or RNA whose nucleotide sequence acts as a guide for the synthesis of a complementary strand

genome

the totality of genetic information belonging to a cell or an organism

chromosome

structure composed of a very long DNA molecule and associated proteins that carries part (or all) of the hereditary information of an organism

homologous chromosome

the maternal and paternal copies of a particular chromosome in a diploid cell

exon

segment of a eukaryotic gene that consists of a sequence of nucleotides that will be represented in mRNA or in a final transfer, ribosomal, or other mature RNA molecule

intron

noncoding region of a eukaryotic gene that is transcribed into an RNA molecule but is then excised by RNA splicing

cell cycle

reproductive cycle of a cell

replication origin

a location on a DNA molecule at which duplication of the DNA begins by the formation of replication forks

centromere

constricted region of a mitotic chromosome that holds sister chromatids together. This is also the site on the DNA where the kinetochore forms so as to capture microtubules from the mitotic spindle.

telomere

end of a chromosome, associated with a characteristic DNA sequence that is replicated in a special way. Counteracts the tendency of the chromosome otherwise to shorten with each round of replication

histone

one of a group of small abundant proteins, rich in arginine and lysine, that combine to form the nucleosome cores around which DNA is wrapped in eukaryotic chromosomes

chromatin

complex of DNA, histones, and non-histone proteins found in the nucleus of a eukaryotic cell. The material of which chromosomes are made

nucleosome

beadlike structure in eukaryotic chromatin, composed of a short length of DNA wrapped around an octameric core of histone proteins. The fundamental structural unit of chromatin

epigenetic inheritance

inheritance of phenotypic changes in a cell or organism that do not result from changes in the nucleotide sequence of DNA

heterochromatin

chromatin that is highly condensed even in interphase; generally transcriptionally inactive

euchromatin

chromatin that isn’t super condensed, generally transcriptionally active

polypeptide backbone

repeating sequences of atoms along the core of the polypeptide chain

side chain

the part of an amino acid that differs between amino acid types; give each type of amino acid its unique chemical and physical properties

conformation

the folded, 3D structure of a polypeptide chain

alpha helix

common folding pattern in proteins, in which a linear sequence of amino acids folds into a right-handed helix stabilized by internal hydrogen bonding between backbone atoms

beta sheet

common structural motif in proteins which different sections of the polypeptide chain run alongside each other, joined by hydrogen-bonding between atoms of the polypeptide backbone

primary structure

linear sequence of monomer units in a polymer (amino acid sequence of a protein)

secondary structure

regular local folding pattern of a polymeric molecule; a helices and b sheets

tertiary structure

complex 3D form of a folded polymer chain, especially a protein or RNA molecule

ligand

any molecule that binds to a specific site on a protein or other molecule

equilibrium constant (K)

the ratio of forward and reverse rate constants for a reaction, equal to the association/affinity constant for a simple binding reaction

enzyme

protein that catalyzes a specific chemical reaction

substrate

molecule on which an enzyme acts

catalyst

substance that can lower the activation energy of a reaction, thus increasing its rate, without being consumed by the reaction

transition state

structure that forms transiently in the course of a chemical reaction and has the highest free energy of any reaction intermediate

coenzyme

small molecule tightly associated with an enzyme that participates in the reaction that the enzyme catalyzes, often by forming a covalent bond to the substrate

feedback inhibition

the process in which a product of a reaction feeds back to inhibit a previous reaction in the same pathway

phosphorylation

reaction in which a phosphate group is covalently coupled to another molecule

active site

region of an enzyme surface to which a substrate molecule binds in order to undergo a catalyzed reaction

regulatory site

region of an enzyme surface to which a regulatory molecule binds and thereby influences the catalytic events at the separate active site

linkage

in ligand binding, the conformational coupling between two separate ligand-binding sites on a protein, such that a conformational change in the protein induced by binding of one ligand affects the binding of a second ligand

cooperativity

regulatory phenomenon in multi-subunit enzymes where the binding of a substrate to one active site affects the binding affinity of other sites, enhancing or inhibiting further substrate binding

protein kinase

enzyme that transfers the terminal phosphate group of ATP to one or more specific amino acids (serine, threonine, or tyrosine) of a target protein

protein phosphatase

enzyme that catalyzes phosphate removal from amino acids of a target protein

scaffold protein

protein that binds groups of intracellular proteins into a complex, often anchoring the complex at a specific location in the cell

proteomics

study of proteomes (similar to genome, set of proteins produced) and their functions

mutation rate

the rate at which changes (mutations) occur in DNA sequences

germ cells

a cell in the germ line of an organism, which includes the haploid gametes and their specified diploid precursor cells. Germ cells contribute to the formation of a new generation of organisms

somatic cells

diploid cells that make up the rest of your body

DNA polymerase

enzyme that synthesizes DNA by joining nucleotides together using a DNA template as a guide

replication fork

Y-shaped region of a replicating DNA molecule; the point at which the two strands of the parent DNA helix are being separated and the daughter strands are being formed

leading strand

one of the two newly synthesized strands of DNA found at a replication fork. Made by continuous synthesis in the 5′-to-3′ direction

lagging strand

one of the two newly synthesized strands of DNA found at a replication fork. Made in discontinuous lengths that are later joined covalently

Okazaki fragments

short DNA segments synthesized discontinuously on the lagging strand during DNA replication, later joined to form a continuous strand

RNA primer

short stretch of RNA synthesized on a DNA template. It is required by DNA polymerases to start their DNA synthesis

DNA primase

enzyme that synthesizes a short strand of RNA on a DNA template, producing an RNA primer for DNA synthesis

proofreading

error-correcting activity of DNA polymerase that ensures newly synthesizes DNA strand is as accurate as possible

DNA ligase

enzyme that joins the ends of two strands of DNA together with a covalent bond to produce one continuous DNA strand using ATP

DNA helicase

unwinds the double helix ahead of the fork using ATP

single-strand DNA-binding proteins

protein that binds to the single strands and prevents helical structures from re-forming while DNA is being replicated

sliding clamp

ring around DNA that keeps polymerase from falling off

clamp loader

uses ATP to open and close the clamp around the DNA

strand-directed mismatch repair

a proofreading system that removes DNA replication errors missed by the DNA polymerase proofreading exonuclease; detects DNA helix distortion and then excises the mismatch in the newly synthesizes strand specifically

DNA topoisomerase I and II

I nicks one strand to relieve supercoiling, no ATP needed; II passes one DNA duplex through a break in another (uses ATP)

origin recognition complex

large protein complex that is bound to the DNA at origins of replication in eukaryotic chromosomes throughout the cell cycle

histone chaperones

protein that binds free histones, releasing them as they are incorporated into newly replicated chromatin

telomerase

enzyme that elongates the telomere sequences in DNA

initiator protein (DnaA/ORC)

binds the origin, opens the A/T-rich DNA to start replication

helicase loader (DnaC/Cdc6+Cdt1)

loads helicase onto origin in an active form

MutS/MutL (or eukaryotic homologs)

mismatch repair, distinguishes new strand from olds

Shelterin

protects telomere ends; helps form T-loop

Post-transcriptional control

any control on gene expression that is exerted at a stage after transcription has begun

alternative RNA splicing

production of different RNAs from the same gene by splicing the transcript in different ways

DNA methylation

addition of methyl groups to DNA. Extensive methylation of the cytosine base in CG sequences is used in plants and animals to help keep genes in an inactive state

attenuation

a gene regulation mechanism in bacteria where the premature termination of transcription is controlled by the rate of translation

CG islands

region of DNA in vertebrate genomes with a greater than average density of CG sequences; the C nucleotides in these regions generally remain unmethylated

riboswitch

a specialized part of a messenger RNA (mRNA) molecule that binds a small target chemical to directly turn gene activity on or off

amino acids

organic molecule containing both an amino group and a carboxyl group

translation

process by which the sequence of nucleotides in an mRNA molecule directs the incorporation of amino acids into protein

genetic code

the set of rules specifying the correspondence between nucleotide triplets (codons) in DNA or RNA and amino acids in proteins

tRNAs

set of small RNA molecules used in protein synthesis as an interface (adaptor) between mRNA and amino acids. Each type of tRNA molecule is covalently linked to a particular amino acid

codon

sequence of three nucleotides in a DNA or mRNA molecule that represents the instruction for incorporation of a specific amino acid into a growing polypeptide chain

open reading frame (ORF)

a continuous nucleotide sequence free from stop codons in at least one of the three reading frames (and thus with the potential to code for protein)

anticodon

sequence of three nucleotides in a transfer RNA (tRNA) molecule that is complementary to a three-nucleotide codon in a messenger RNA (mRNA) molecule

wobble pair

pairing at the third position of the codon and the first position of the anticodon is more flexible. This flexibility allows for certain non-standard base pairings to occur

tRNA chemical modifications

things like methylation, thiolation, deamination, hydroxylation, which can stabilize the tRNA